Parallel reactor with internal sensing and method of using same

ABSTRACT

Devices and methods for controlling and monitoring the progress and properties of multiple reactions are disclosed. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial libraries, but also offer significant advantages over conventional experimental reactors as well. The apparatus generally includes multiple vessels for containing reaction mixtures, and systems for controlling the stirring rate and temperature of individual reaction mixtures or groups of reaction mixtures. In addition, the apparatus may include provisions for independently controlling pressure in each vessel, and a system for injecting liquids into the vessels at a pressure different than ambient pressure. In situ monitoring of individual reaction mixtures provides feedback for process controllers, and also provides data for determining reaction rates, product yields, and various properties of the reaction products, including viscosity and molecular weight. Computer-based methods are disclosed for process monitoring and control, and for data display and analysis.

CROSS REFERENCE TO RELATED APPLICATIONS

Under 35 U.S.C. §119, this application claims the benefit of a foreignpriority application in the PCT, Ser. No. PCT/US99/18358, filed Aug. 12,1999, which is a continuation-in-part (and claims the benefit ofpriority under 35 U.S.C. §120) of 09/239,223, filed Jan. 29, 1999, and acontinuation-in-part of U.S. application Ser. No. 09/211,982, filed Dec.14, 1998, now U.S. Pat. No. 6,306,658, which is a continuation in partof U.S. application Ser. No. 09/177,170, filed Oct. 22, 1998, whichclaims the benefit of U.S. Provisional application Ser. No. 60/096,603,filed Aug. 13, 1998. The disclosures of the prior applications areconsidered part of and are incorporated by reference in their entiretyherein, the disclosure of this application.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention relates to methods, devices, and computer programsfor rapidly making, screening, and characterizing an array of materialsin which process conditions are controlled and monitored.

2. Discussion

In combinatorial chemistry, a large number of candidate materials arecreated from a relatively small set of precursors and subsequentlyevaluated for suitability for a particular application. As currentlypracticed, combinatorial chemistry permits scientists to systematicallyexplore the influence of structural variations in candidates bydramatically accelerating the rates at which they are created andevaluated. Compared to traditional discovery methods, combinatorialmethods sharply reduce the costs associated with preparing and screeningeach candidate.

Combinatorial chemistry has revolutionized the process of drugdiscovery. One can view drug discovery as a two-step process: acquiringcandidate compounds through laboratory synthesis or through naturalproducts collection, followed by evaluation or screening for efficacy.Pharmaceutical researchers have long used high-throughput screening(HTS) protocols to rapidly evaluate the therapeutic value of naturalproducts and libraries of compounds synthesized and cataloged over manyyears. However, compared to HTS protocols, chemical synthesis hashistorically been a slow, arduous process. With the advent ofcombinatorial methods, scientists can now create large libraries oforganic molecules at a pace on par with HTS protocols.

Recently, combinatorial approaches have been used for discovery programsunrelated to drugs. For example, some researchers have recognized thatcombinatorial strategies also offer promise for the discovery ofinorganic compounds such as high-temperature superconductors,magnetoresistive materials, luminescent materials, and catalyticmaterials. See, for example, co-pending U.S. patent application Ser. No.08/327,513 “The Combinatorial Synthesis of Novel Materials” (publishedas WO 96/11878) and co-pending U.S. patent application Ser. No.08/898,715 “Combinatorial Synthesis and Analysis of OrganometallicCompounds and Catalysts” (published, in part, as WO 98/03251), which areall herein incorporated by reference.

Because of its success in eliminating the synthesis bottleneck in drugdiscovery, many researchers have come to narrowly view combinatorialmethods as tools for creating structural diversity. Few researchers haveemphasized that, during synthesis, variations in temperature, pressure,ionic strength, and other process conditions can strongly influence theproperties of library members. For instance, reaction conditions areparticularly important in formulation chemistry, where one combines aset of components under different reaction conditions or concentrationsto determine their influence on product properties.

Moreover, because the performance criteria in materials science is oftendifferent than in pharmaceutical research, many workers have failed torealize that process variables often can be used to distinguish amonglibrary members both during and after synthesis. For example, theviscosity of reaction mixtures can be used to distinguish librarymembers based on their ability to catalyze a solution-phasepolymerization-at constant polymer concentration, the higher theviscosity of the solution, the greater the molecular weight of thepolymer formed. Furthermore, total heat liberated and/or peaktemperature observed during an exothermic reaction can be used to rankcatalysts.

Therefore, a need exists for an apparatus to prepare and screencombinatorial libraries in which one can monitor and control processconditions during synthesis and screening.

SUMMARY OF THE INVENTION

The present invention generally provides an apparatus for parallelprocessing of reaction mixtures. The apparatus includes vessels forcontaining the reaction mixtures, a stirring system, and a temperaturecontrol system that is adapted to maintain individual vessels or groupsof vessels at different temperatures. The apparatus may consist of amonolithic reactor block, which contains the vessels, or an assemblageof reactor block modules. A robotic material handling system can be usedto automatically load the vessels with starting materials. In additionto heating or cooling individual vessels, the entire reactor block canbe maintained at a nearly uniform temperature by circulating atemperature-controlled thermal fluid through channels formed in thereactor block. The stirring system generally includes stirringmembers—blades, bars, and the like—placed in each of the vessels, and amechanical or magnetic drive mechanism. Torque and rotation rate can becontrolled and monitored through strain gages, phase lag measurements,and speed sensors.

The apparatus may optionally include a system for evaluating materialproperties of the reaction mixtures. The system includes mechanicaloscillators located within the vessels. When stimulated with avariable-frequency signal, the mechanical oscillators generate responsesignals that depend on properties of the reaction mixture. Throughcalibration, mechanical oscillators can be used to monitor molecularweight, specific gravity, elasticity, dielectric constant, conductivity,and other material properties of the reaction mixtures.

The present invention also provides an apparatus for monitoring rates ofproduction or consumption of a gas-phase component of a reactionmixture. The apparatus generally comprises a closed vessel forcontaining the reaction mixture, a stirring system, a temperaturecontrol system and a pressure control system. The pressure controlsystem includes a pressure sensor that communicates with the vessel, aswell as a valve that provides venting of a gaseous product from thevessel. In addition, in cases where a gas-phase reactant is consumedduring reaction, the valve provides access to a source of the reactant.Pressure monitoring of the vessel, coupled with venting of product orfilling with reactant allows the investigator to determine rates ofproduction or consumption, respectively.

One aspect of the present invention provides an apparatus for monitoringrates of consumption of a gas-phase reactant. The apparatus generallycomprises a closed vessel for containing the reaction mixture, astirring system, a temperature control system and a pressure controlsystem. The pressure control system includes a pressure sensor thatcommunicates with the vessel, as well as a flow sensor that monitors theflow rate of reactant entering the vessel. Rates of consumption of thereactant can be determined from the reactant flow rate and filling time.

The present invention also provides a method of making andcharacterizing a plurality of materials. The method includes the stepsof providing vessels with starting materials to form reaction mixtures,confining the reaction mixtures in the vessels to allow the reaction tooccur, and stirring the reaction mixtures for at least a portion of theconfining step. The method further includes the step of evaluating thereaction mixtures by tracking at least one characteristic of thereaction mixtures for at least a portion of the confining step. Variouscharacteristics or properties can be monitored during the evaluatingstep, including temperature, rate of heat transfer, conversion ofstarting materials, rate of conversion, torque at a given stirring rate,stall frequency, viscosity, molecular weight, specific gravity,elasticity, dielectric constant, and conductivity.

One aspect of the present invention provides a method of monitoring therate of consumption of a gas-phase reactant. The method comprises thesteps of providing a vessel with starting materials to form the reactionmixture, confining the reaction mixtures in the vessel to allow reactionto occur, and stirring the reaction mixture for at least a portion ofthe confining step. The method further includes filling the vessel withthe gas-phase reactant until gas pressure in the vessel exceeds anupper-pressure limit, P_(H), and allowing gas pressure in the vessel todecay below a lower-pressure limit, P_(L). Gas pressure in the vessel ismonitored and recorded during the addition and consumption of thereactant. This process is repeated at least once, and rates ofconsumption of the gas-phase reactant in the reaction mixture aredetermined from the pressure versus time record.

Another aspect of the present invention provides a method of monitoringthe rate of production of a gas-phase product. The method comprises thesteps of providing a vessel with starting materials to form the reactionmixture, confining the reaction mixtures in the vessel to allow reactionto occur, and stirring the reaction mixture for at least a portion ofthe confining step. The method also comprises the steps of allowing gaspressure in the vessel to rise above an upper-pressure limit, P_(H), andventing the vessel until gas pressure in the vessel falls below alower-pressure limit, P_(L). The gas pressure in the vessel is monitoredand recorded during the production of the gas-phase component andsubsequent venting of the vessel. The process is repeated at least once,so rates of production of the gas-phase product can be calculated fromthe pressure versus time record.

The present invention provides an apparatus for parallel processing ofreaction mixtures comprising vessels for containing the reactionmixtures, a stirring system for agitating the reaction mixtures, atemperature control system for regulating the temperature of thereaction mixtures, and a fluid injection system. The vessels are sealedto minimize unintentional gas flow into or out of the vessels, and thefluid injection system allows introduction of a liquid into the vesselsat a pressure different than ambient pressure. The fluid injectionsystem includes fill ports that are adapted to receive a liquid deliveryprobe, such as a syringe or pipette, and also includes conduits, valves,and tubular injectors. The conduits provide fluid communication betweenthe fill ports and the valves and between the valves and the injectors.The injectors are located in the vessels, and can have varying lengths,depending on whether fluid injection is to occur in the reactionmixtures or in the vessel headspace above the reaction mixtures.Generally, a robotic material handling system manipulates the fluiddelivery probe and controls the valves. The injection system can be usedto deliver gases, liquids, and slurries, e.g., catalysts on solidsupports.

One aspect of the present invention provides an apparatus for parallelprocessing of reaction mixtures comprising sealed vessels, a temperaturecontrol system, and a stirring system having a magnetic feed throughdevice for coupling an external drive mechanism with a spindle that iscompletely contained within one of the vessels. The magnetic feedthrough device includes a rigid pressure barrier having a cylindricalinterior surface that is open along the base of the pressure barrier.The base of the pressure barrier is attached to the vessel so that theinterior surface of the pressure barrier and the vessel define a closedchamber. The magnetic feed through device further includes a magneticdriver that is rotatably mounted on the rigid pressure barrier and amagnetic follower that is rotatably mounted within the pressure barrier.The drive mechanism is mechanically coupled to the magnetic driver, andone end of the spindle is attached to a leg portion of the magneticfollower that extends into the vessel headspace. Since the magneticdriver and follower are magnetically coupled, rotation of the magneticdriver induces rotation of the magnetic follower and spindle.

Another aspect of the present invention provides an apparatus forparallel processing of reaction mixtures comprising sealed vessels, atemperature control system, and a stirring system that includesmulti-piece spindles that are partially contained in the vessels. Eachof the spindles includes an upper spindle portion that is mechanicallycoupled to a drive mechanism, a removable stirrer contained in one ofthe vessels, and a coupler for reversibly attaching the removablestirrer to the upper spindle portion. The removable stirrer is made of achemically resistant plastic material, such as polyethylethylketone orpolytetrafluoroethylene, and is typically discarded after use.

The exact combination of parallel processing features depends on theembodiment of the invention being practiced. In some aspects, thepresent invention provides an apparatus for parallel processing ofreaction mixtures comprising sealed vessels and an injection system. Thepresent invention also provides an apparatus for parallel processing ofreaction mixtures comprising sealed vessels, an injection system and astirring system. The present invention also provides an apparatus forparallel processing of reaction mixtures comprising vessels having atemperature control system and a stirring system. The present inventionalso provides an apparatus for parallel processing of reaction mixturescomprising sealed vessels and a pressure control system. The presentinvention also provides an apparatus for parallel processing of reactionmixtures comprising sealed vessels, an injection system and a system forproperty or characteristic monitoring.

The present invention also provides computer programs andcomputer-implemented methods for monitoring the progress and propertiesof parallel chemical reactions. In one aspect, the invention features amethod of monitoring a combinatorial chemical reaction. The methodincludes (a) receiving a measured value associated with the contents ofeach of a plurality of reactor vessels; (b) displaying the measuredvalues; and (c) repeating steps (a) and (b) multiple times over thecourse of the combinatorial chemical reaction.

Implementations of the invention can include one or more of thefollowing advantageous features. The measured values include a set ofvalues for a number of reaction conditions associated with each of thereactor vessels. Step (c) is performed at a predetermined sampling rate.The method also includes changing a reaction parameter associated withone of the reactor vessels in response to the measured value to maintainthe reactor vessel at a predetermined set point. Reaction parametersinclude temperature, pressure, and motor (stirring) speed. The methodalso includes quenching a reaction in one of the reactor vessels inresponse to the measured value associated with the contents of thereactor vessel. The method also includes using the measured value tocalculate an experimental variable or value for one of the reactorvessels. Examples of experimental variables include rates of change oftemperature or pressure, percent conversion of a starting material, andviscosity. The method also includes displaying the experimentalvariable.

In general, in another aspect, the invention features a method forcontrolling a combinatorial chemical reactor including multiple reactorvessels, each containing a reaction environment. The method includesreceiving a set point for a property associated with each vessel'sreaction environment; measuring a set of experimental values for theproperty for each vessel; displaying the set of experimental values; andchanging the reaction environment in one or more of the plurality ofreactor vessels in response to the set point and a change in one or moreof the set of experimental values. For example, the method may terminatea reaction (change the reaction environment) in response to reactantconversion (experimental value) indicating that a target conversion (setpoint) has been reached. During reaction, a graphical representation ofthe set of experimental values is displayed, often as a histogram.

In general, in another aspect, the invention features a computer programon a computer-readable medium for monitoring a combinatorial chemicalreaction. The program includes instructions to (a) receive a measuredvalue associated with the contents of each of a plurality of reactorvessels, instructions to (b) display the measured values, andinstructions to (c) repeat steps (a) and (b) multiple times during thecourse of the combinatorial chemical reaction. The computer programincludes instructions to change a reaction parameter associated with oneof the reactor vessels in response to the measured value to maintain thereactor vessel at a predetermined set point.

In general, in another aspect, the invention features a reactor controlsystem for monitoring and controlling parallel chemical reactions. Thereactor system includes a system control module for providing controlsignals to a parallel chemical reactor including multiple reactorvessels, a mixing monitoring and control system, a temperaturemonitoring and control system, and a pressure monitoring and controlsystem. The reactor system also includes a data analysis module forreceiving a set of measured values from the parallel chemical reactorand for calculating one or more calculated values for each of thereactor vessels. In addition, the reactor control system includes a userinterface module for receiving reaction parameters and for displayingthe set of measured values and calculated values.

Advantages that can be seen in implementations of the invention includeone or more of the following. Process variables can be monitored andcontrolled for multiple elements in a combinatorial library as achemical reaction progresses. Data can be extracted for each libraryelement repeatedly and in parallel over the course of the reaction,instead of extracting only a limited number of data points for selectedlibrary elements. Calculations and corrections can be appliedautomatically to every available data point for every library elementover the course of the reaction. A single experimental value can becalculated from the entire data set for each library element.

Another aspect of the present invention involves a method of making andcharacterizing materials. The method comprises forming chemical reactionmixtures in a plurality of reactor vessels of a parallel reactorapparatus. The apparatus comprises sensors for providing measured valuesrelating to chemical reactions in the reactor vessels and a processorfor receiving data relating to the measured values. The method alsocomprises confining the reaction mixture in each reactor vessel againstfluid communication with the other vessels and at a pressure other thanambient pressure. The method further comprises injecting a fluid into atleast one of the reactor vessels while the reaction mixture in the atleast one vessel is confined and at a pressure other than ambientpressure. The method also comprises agitating the reaction mixtures forat least a portion of the confining step and using the processor toreceive the data relating to the measured values of the chemicalreactions in the reactor vessels.

In yet another aspect of the present invention, a method of making andcharacterizing materials comprises forming chemical reaction mixtures,confining the reaction mixtures in reactor vessels, injecting a fluidinto at least one of the reactor vessels and agitating the reactionmixtures, generally as set forth in the preceding paragraph. The methodfurther comprises using the processor to receive and display the datarelating to the measured values and comparing at least onecharacteristics of the chemical reactions in the reactor vessels basedon the data.

The present invention is also directed to parallel processing apparatuscomprising a plurality of sealed reactor vessels for holding reactionmixtures and a temperature control system for regulating the temperatureof the reaction mixtures in the reactor vessels. The apparatus furthercomprises an injection system for introducing chemical reactionmaterials into one or more of the sealed reactor vessels while thereactor vessel is at a pressure other than ambient pressure. Theapparatus also comprises a mechanism for agitating the reaction mixturein each of the sealed reactor vessels, sensors for providing measuredvalues relating to chemical reactions in the reactor vessels, and aprocessor for receiving and comparing data relating to the measuredvalues.

In another aspect of the present invention, parallel processingapparatus comprises a plurality of sealed reactor vessels for holdingreaction mixtures, temperature control means for regulating thetemperature of the reaction mixtures in the reactor vessels and aninjection means for introducing chemical reaction materials into one ormore of the sealed reactor vessels. The apparatus further comprisesmeans for agitating the reaction mixture in each of the sealed reactorvessels, means for sensing measured values relating to chemicalreactions in the reactor vessels, and means for receiving and comparingdata relating to the measured values.

In yet another aspect of the present invention, an apparatus for theparallel processing of reaction mixtures comprises a plurality of sealedreactor vessels, temperature control means, injection means, means foragitating the reaction mixture in each reaction vessel, and means forsensing measured values, generally as set forth in the precedingparagraph. The apparatus further comprises means for receiving anddisplaying data relating to the measured values.

A further understanding of the nature and advantages of the presentinvention may be realized by reference to the remaining portions of thespecification, drawings, and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a parallel reactor system in accordance with thepresent invention.

FIG. 2 shows a perspective view of a modular reactor block with arobotic liquid handling system.

FIG. 3 shows a temperature monitoring system.

FIG. 4 shows a cross-sectional view of an integral temperaturesensor-vessel assembly.

FIG. 5 shows a side view of an infrared temperature measurement system.

FIG. 6 shows a temperature monitoring and control system for a reactorvessel.

FIG. 7 illustrates another temperature control system, which includesliquid cooling and heating of the reactor block.

FIG. 8 is a cross-sectional view of thermoelectric devices sandwichedbetween a reactor block and heat transfer plate.

FIG. 9 is a cross-sectional view of a portion of a reactor block usefulfor obtaining calorimetric data.

FIG. 10 is an exploded perspective view of a stirring system for asingle module of a modular reactor block of the type shown in FIG. 2.

FIG. 11 is a schematic representation of an electromagnetic stirringsystem.

FIGS. 12-13 are schematic representations of portions of electromagnetstirring arrays in which the ratios of electromagnets to vessel sitesapproach 1:1 and 2:1, respectively, as the number of vessel sitesbecomes large.

FIG. 14 is a schematic representation of an electromagnet stirring arrayin which the ratio of electromagnets to vessel sites is 4:1.

FIG. 15 shows additional elements of an electromagnetic stirring system,including drive circuit and processor.

FIG. 16 illustrates the magnetic field direction of a 2×2 electromagnetarray at four different times during one rotation of a magnetic stirringbar.

FIG. 17 illustrates the magnetic field direction of a 4×4 electromagnetarray at five different times during one full rotation of a 3×3 array ofmagnetic stirring bars.

FIG. 18 illustrates the rotation direction of the 3×3 array of magneticstirring bars shown in FIG. 17.

FIG. 19 shows a wiring configuration for an electromagnetic stirringsystem.

FIG. 20 shows an alternate wiring configuration for an electromagneticstirring system.

FIG. 21 shows the phase relationship between sinusoidal source currents,I_(A)(t) and I_(B)(t), which drive two series of electromagnets shown inFIGS. 19 and 20.

FIG. 22 is a block diagram of a power supply for an electromagneticstirring system.

FIG. 23 illustrates an apparatus for directly measuring the appliedtorque of a stirring system.

FIG. 24 shows placement of a strain gauge in a portion of a base platethat is similar to the lower plate of the reactor module shown in FIG.10.

FIG. 25 shows an inductive sensing coil system for detecting rotationand measuring phase angle of a magnetic stirring blade or bar.

FIG. 26 shows typical outputs from inductive sensing coils, whichillustrate phase lag associated with magnetic stirring for low and highviscosity solutions, respectively.

FIG. 27 illustrates how amplitude and phase angle will vary during areaction as the viscosity increases from a low value to a valuesufficient to stall the stirring bar.

FIGS. 28-29 show bending modes of tuning forks and bimorph/unimorphresonators, respectively.

FIG. 30 schematically shows a system for measuring the properties ofreaction mixtures using mechanical oscillators.

FIG. 31 shows an apparatus for assessing reaction kinetics based onmonitoring pressure changes due to production or consumption variousgases during reaction.

FIG. 32 shows results of calibration runs for polystyrene-toluenesolutions using mechanical oscillators.

FIG. 33 shows a calibration curve obtained by correlating M_(W) of thepolystyrene standards with the distance between the frequency responsecurve for toluene and each of the polystyrene solutions of FIG. 32.

FIG. 34 depicts the pressure recorded during solution polymerization ofethylene to polyethylene.

FIGS. 35-36 show ethylene consumption rate as a function of time, andthe mass of polyethylene formed as a function of ethylene consumed,respectively.

FIG. 37 shows a perspective view of an eight-vessel reactor module, ofthe type shown in FIG. 10, which is fitted with an optional liquidinjection system.

FIG. 38 shows a cross sectional view of a first embodiment of a fillport having an o-ring seal to minimize liquid leaks.

FIG. 39 shows a second embodiment of a fill port.

FIG. 40 shows a phantom front view of an injector manifold.

FIG. 40A shows a perspective view of an injector manifold 1006

FIG. 40B shows a cross sectional view of the injector manifold shown inFIG. 40A.

FIGS. 41-42 show a cross sectional view of an injector manifold alongfirst and second section lines shown in FIG. 40, respectively.

FIG. 43 shows a phantom top view of an injector adapter plate, whichserves as an interface between an injector manifold and a block of areactor module shown in FIG. 37.

FIG. 44 shows a cross sectional side view of an injector adapter platealong a section line shown in FIG. 43.

FIG. 45 shows an embodiment of a well injector.

FIG. 46 shows a top view of a reactor module.

FIG. 47 shows a “closed” state of an injector system valve prior tofluid injection.

FIG. 48 shows an “open” state of an injector system valve prior duringfluid injection, and shows a stirring mechanism and associated seals formaintaining above-ambient pressure in reactor vessels.

FIG. 49 shows a cross sectional view of a magnetic feed through stirringmechanism that helps minimize gas leaks associated with dynamic seals.

FIG. 50 shows a perspective view of a stirring mechanism shown in FIG.48, and provides details of a multi-piece spindle.

FIG. 50A shows an alternative design for a multi-piece spindle.

FIG. 50B shows details of the alternative design for a multi-piecespindle shown in FIG. 50B.

FIG. 51 shows details of a coupler portion of a multi-piece spindle.

FIG. 52 shows a cross sectional view of the coupler shown in FIG. 51.

FIG. 53 is a block diagram of a data processing system showing animplementation of the invention.

FIGS. 54-57 are schematic diagrams of a parallel reactor suitable foruse with the invention.

FIG. 58 is a flow diagram of a method of controlling and analyzing aparallel chemical reaction.

FIG. 59 is an illustration of a dialog window for user input of systemconfiguration information.

FIG. 60 is an illustration of a dialog window for user input of datadisplay information.

FIG. 61 is an illustration of a dialog window for user input of parallelreactor parameters.

FIG. 62 is an illustration of a dialog window for user input of atemperature gradient for reactor blocks in a parallel reactor.

FIGS. 63-64 are illustrations of windows displaying system status andexperimental results for a parallel reactor.

FIG. 65 is an illustration of a window displaying experimental resultsfor a single reactor vessel.

FIG. 66 is an illustration of a dialog window for user input of colorscaling parameters.

FIG. 67 is a schematic diagram of a computer platform suitable forimplementing the data processing system of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides an apparatus, methods, and computerprograms for carrying out and monitoring the progress and properties ofmultiple reactions in situ. It is especially useful for synthesizing,screening, and characterizing combinatorial libraries, but offerssignificant advantages over conventional experimental reactors as well.For example, in situ monitoring of individual reaction mixtures not onlyprovides feedback for process controllers, but also provides data fordetermining reaction rates, product yields, and various properties ofthe reaction products, including viscosity and molecular weight duringan experiment. Moreover, in situ monitoring coupled with tight processcontrol can improve product selectivity, provide opportunities forprocess and product optimization, allow processing oftemperature-sensitive materials, and decrease experimental variability.

Other advantages result from using small mixture volumes. In addition toconserving valuable reactants, decreasing sample size increases surfacearea relative to volume within individual reactor vessels. This improvesthe uniformity of reaction mixtures, aids gas-liquid exchange inmultiphase reactions, and increases heat transfer between the samplesand the reactor vessels. Because large samples respond much slower tochanges in system conditions, the use of small samples, along with insitu monitoring and process control, also allows for time-dependentprocessing and characterization.

The parallel reactor of this invention is useful for the research anddevelopment of chemical reactions, catalysts and processes. The sametype of reaction may be preformed in each vessel or different reactionsmay be performed in each vessel. Thus, each reaction vessel may varywith regard to its contents during an experiment. Each reaction vesselcan vary by a process condition, including catalyst amounts (volume,moles or mass), ratios of starting components, time for reaction,reaction temperature, reaction pressure, rate of reactant addition tothe reaction, reaction atmosphere, reaction stir rate, injection of acatalyst or reactant or other component (e.g., a reaction quencher) andother conditions that those of skill in the art will recognize. Eachreaction vessel can also vary by the chemicals present, such as by usingdifferent reactants or catalysts in two or more vessels.

For example, the parallel reactor of this invention may have reactionvessels that are of different volume. The reactor vessel volume may varyfrom about 0.1 milliliter (ml) to about 500 ml, more particularly fromabout 1 ml to about 100 ml and even more particularly from about 5 ml toabout 20 ml. These reactor vessel sizes allow for reactant volumes in arange that functionally allow for proper stirring (e.g., a 15 ml reactorvessel allows for reactant volumes of between about 2-10 ml). Also, theparallel reactor of this invention allows the reactor pressure to varyfrom vessel to vessel or module to module or cell to cell, with eachvessel being at a pressure in the range of from about atmosphericpressure to about 500 psi and more particularly in the range of fromatmospheric to about 300 psi. In still other embodiments, the reactortemperature may vary from vessel to vessel or module to module or cellto cell, with each vessel being at a temperature in the range of fromabout −150° C. to about 250° C. and more particularly in the range offrom −100° C. to about 200° C. The stirring rates may also vary fromvessel to vessel or module to module or cell to cell, with each vesselbeing stirred by mechanical stirring at a rate of from about 0 to about3000 revolutions per minute (rpm) and more particularly at a rate offrom about 10 to about 2000 rpm and even more particularly at a rate offrom about 100 to about 1000 rpm. In other embodiments, the parallelreactor of this invention allows for the injection of reactants or othercomponents (such as catalysts) while a reactor vessel is at reactionpressure (as discussed in detail below). Generally, the injection ofreactants or components allows for the reaction conditions to be variedfrom vessel to vessel, such as by adding a reaction quencher at a timedfrequency or a conversion frequency. Reaction times can vary dependingon the experiment being performed, but may be in the range from lessthan one minute to about 48 hours, more particularly in the range offrom about one minute to about 24 hours and even more particularly inthe range of from about 5 minutes to about 12 hours.

Overview of Parallel Reactor

The parallel reactor system of the present invention is an integratedplatform for effecting combinatorial research in chemistry and materialsscience applications. An integrated parallel reactor system comprises aplurality of reactors that can be operated in parallel on a scalesuitable for research applications—typically bench scale or smallerscale (e.g., mini-reactors and micro-reactors). The reactors of such anintegrated system can typically, but not necessarily, be formed in, beintegral with or be linked by a common substrate, be arranged in acommon plane, preferably with spatial uniformity, and/or can share acommon support structure or housing. The integrated parallel reactorsystem can also include one or more control and monitoring systems thatare fully or partially integral therewith.

FIG. 1 shows one embodiment of a parallel reactor system 100. Thereactor system 100 includes removable vessels 102 for receivingreactants. Wells 104 formed into a reactor block 106 contain the vessels102. Although the wells 104 can serve as reactor vessels, removablevessels 102 or liners provide several advantages. For example, followingreaction and preliminary testing (screening), one can remove a subset ofvessels 102 from the reactor block 106 for further in-depthcharacterization. When using removable vessels 102, one can also selectvessels 102 made of material appropriate for a given set of reactants,products, and reaction conditions. Unlike the reactor block 106, whichrepresents a significant investment, the vessels 102 can be discarded ifdamaged after use. Finally, one can lower system 100 costs and ensurecompatibility with standardized sample preparation and testing equipmentby designing the reactor block 106 to accommodate commercially availablevessels.

As shown in FIG. 1, each of the vessels 102 contains a stirring blade108. In one embodiment, each stirring blade 108 rotates at about thesame speed, so that each of the reaction mixtures within the vessels 102experience similar mixing. Because reaction products can be influencedby mixing intensity, a uniform rotation rate ensures that anydifferences in products does not result from mixing variations. Inanother embodiment, the rotation rate of each stirring blade 108 can bevaried independently, which as discussed below, can be used tocharacterize the viscosity and molecular weight of the reaction productsor can be used to study the influence of mixing speed on reaction.

Depending on the nature of the starting materials, the types ofreactions, and the method used to characterize reaction products andrates of reaction, it may be desirable to enclose the reactor block 106in a chamber 110. The chamber 10 may be evacuated or filled with asuitable gas. In some cases, the chamber 110 may be used only during theloading of starting materials into the vessels 102 to minimizecontamination during sample preparation, for example, to preventpoisoning of oxygen sensitive catalysts. In other cases, the chamber 110may be used during the reaction process or the characterization phase,providing a convenient method of supplying one or more gases to all ofthe vessels 102 simultaneously. In this way, a gaseous reactant can beadded to all of the vessels 102 at one time. Note, however, it is oftennecessary to monitor the rate of disappearance of a gaseous reactant—forexample, when determining rates of conversion—and in such cases thevessels 102 are each sealed and individually connected to a gas source,as discussed below.

FIG. 2 shows a perspective view of a parallel reactor system 130comprised of a modular reactor block 132. The modular reactor block 132shown in FIG. 2 consists of six modules 134, and each module 134contains eight vessels (not shown). Note, however, the number of modules134 and the number of vessels within each of the modules 134 can vary.In some embodiments, a module 134 may be broken down into componentcells (not shown), for example with each cell containing one well 104holding a reaction vessel 102. Thus, if a module is to contain eightreaction vessels, there may be eight cells, which facilitates lower costmanufacturing as well as replacement of damaged or worn cells. There mayany number of cells per module, such as cell that contains two reactionvessels per cell, etc.

The use of modules 134 offers several advantages over a monolithicreactor block. For example, the size of the reactor block 132 can beeasily adjusted depending on the number of reactants or the size of thecombinatorial library. Also, relatively small modules 134 are easier tohandle, transport, and fabricate than a single, large reactor block. Adamaged module can be quickly replaced by a spare module, whichminimizes repair costs and downtime. Finally, the use of modules 134improves control over reaction parameters. For instance, stirring speed,temperature, and pressure of each of the vessels can be varied betweenmodules.

In the embodiment shown in FIG. 2, each of the modules 134 is mounted ona base plate 136 having a front 138 and a rear 140. The modules 134 arecoupled to the base plate 136 using guides (not shown) that mate withchannels 142 located on the surface of the base plate 136. The guidesprevent lateral movement of the modules 134, but allow linear travelalong the channels 142 that extend from the front 138 toward the rear140 of the base plate 136. Stops 144 located in the channels 142 nearthe front 138 of the base plate 136 limit the travel of the modules 134.Thus, one or more of the modules 134 can be moved towards the front 138of the base plate 136 to gain access to individual vessels while theother modules 134 undergo robotic filling. In another embodiment, themodules 134 are rigidly mounted to the base plate 136 using bolts,clips, or other fasteners.

As illustrated in FIG. 2, a conventional robotic material handlingsystem 146 is ordinarily used to load vessels with starting materials.The robotic system 146 includes a pipette or probe 148 that dispensesmeasured amounts of liquids into each of the vessels. The robotic system146 manipulates the probe 148 using a 3-axis translation system 150. Theprobe 148 is connected to sources 152 of liquid reagents throughflexible tubing 154. Pumps 156, which are located along the flexibletubing 154, are used to transfer liquid reagents from the sources 152 tothe probe 148. Suitable pumps 156 include peristaltic pumps and syringepumps. A multi-port valve 158 located downstream of the pumps 156selects which liquid reagent from the sources 152 is sent to the probe148 for dispensing in the vessels.

The robotic fluid handling system 146 is controlled by a processor 160.In the embodiment shown in FIG. 2, the user first supplies the processor160 with operating parameters using a software interface. Typicaloperating parameters include the coordinates of each of the vessels andthe initial compositions of the reaction mixtures in individual vessels.The initial compositions can be specified as lists of liquid reagentsfrom each of the sources 152, or as incremental additions of variousliquid reagents relative to particular vessels.

Temperature Control and Monitoring

The ability to monitor and control the temperature of individual reactorvessels is an important aspect of the present invention. Duringsynthesis, temperature can have a profound effect on structure andproperties of reaction products. For example, in the synthesis oforganic molecules, yield and selectivity often depend strongly ontemperature. Similarly, in polymerization reactions, polymer structureand properties—molecular weight, particle size, monomer conversion,microstructure—can be influenced by reaction temperature. Duringscreening or characterization of combinatorial libraries, temperaturecontrol and monitoring of library members is often essential to makingmeaningful comparisons among members. Finally, temperature can be usedas a screening criteria or can be used to calculate useful process andproduct variables. For instance, catalysts of exothermic reactions canbe ranked based on peak reaction temperature and/or total heat releasedover the course of reaction, and temperature measurements can be used tocompute rates of reaction and conversion.

FIG. 3 illustrates one embodiment of a temperature monitoring system180, which includes temperature sensors 182 that are in thermal contactwith individual vessels 102. For clarity, we describe the temperaturemonitoring system 180 with reference to the monolithic reactor block 106of FIG. 1, but this disclosure applies equally well to the modularreactor block 132 of FIG. 2. Suitable temperature sensors 182 includejacketed or non-jacketed thermocouples (TC), resistance thermometricdevices (RTD), and thermistors. The temperature sensors 182 communicatewith a temperature monitor 184, which converts signals received from thetemperature sensors 182 to a standard temperature scale. An optionalprocessor 186 receives temperature data from the temperature monitor184. The processor 186 performs calculations on the data, which mayinclude wall corrections and simple comparisons between differentvessels 102, as well as more involved processing such as calorimetrycalculations discussed below. During an experimental run, temperaturedata is typically sent to storage 188 so that it can be retrieved at alater time for analysis.

FIG. 4 shows a cross-sectional view of an integral temperaturesensor-vessel assembly 200. The temperature sensor 202 is embedded inthe wall 204 of a reactor vessel 206. The surface 208 of the temperaturesensor 202 is located adjacent to the inner wall 210 of the vessel toensure good thermal contact between the contents of the vessel 206 andthe temperature sensor 202. The sensor arrangement shown in FIG. 3 isuseful when it is necessary to keep the contents of the reactor vessel206 free of obstructions. Such a need might arise, for example, whenusing a freestanding mixing device, such as a magnetic stirring bar.Note, however, that fabricating an integral temperature sensor such asthe one shown in FIG. 4 can be expensive and time consuming, especiallywhen using glass reactor vessels.

Thus, in another embodiment, the temperature sensor is immersed in thereaction mixture. Because the reaction environment within the vessel mayrapidly damage the temperature sensor, it is usually jacketed with aninert material, such as a fluorinated thermoplastic. In addition to lowcost, direct immersion offers other advantages, including rapid responseand improved accuracy. In still another embodiment, the temperaturesensor is placed on the outer surface 212 of the reactor vessel of FIG.4. As long as the thermal conductivity of the reactor vessel is known,relatively accurate and rapid temperature measurements can be made.

One can also remotely monitor temperature using an infrared systemillustrated in FIG. 5. The infrared monitoring system 230 comprises anoptional isolation chamber 232, which contains the reactor block 234 andvessels 236. The top 238 of the chamber 232 is fitted with a window 240that is transparent to infrared radiation. An infrared-sensitive camera242 positioned outside the isolation chamber 232, detects and recordsthe intensity of infrared radiation passing through the window 240.Since infrared emission intensity depends on source temperature, it canbe used to distinguish high temperature vessels from low temperaturevessels. With suitable calibration, infrared intensity can be convertedto temperature, so that at any given time, the camera 242 provides“snapshots” of temperature along the surface 244 of the reactor block234. In the embodiment shown in FIG. 5, the tops 246 of the vessels 236are open. In an alternate embodiment, the tops 246 of the vessels 236are fitted with infrared transparent caps (not shown). Note that, withstirring, the temperature is uniform within a particular vessel, andtherefore the surface temperature of the vessel measured by infraredemission will agree with the bulk temperature measured by a TC or RTDimmersed in the vessel.

The temperature of the reactor vessels and block can be controlled aswell as monitored. Depending on the application, each of the vessels canbe maintained at the same temperature or at different temperaturesduring an experiment. For example, one may screen compounds forcatalytic activity by first combining, in separate vessels, each of thecompounds with common starting materials; these mixtures are thenallowed to react at uniform temperature. One may then furthercharacterize a promising catalyst by combining it in numerous vesselswith the same starting materials used in the screening step. Themixtures then react at different temperatures to gauge the influence oftemperature on catalyst performance (speed, selectivity). In manyinstances, it may be necessary to change the temperature of the vesselsduring processing. For example, one may decrease the temperature of amixture undergoing a reversible exothermic reaction to maximizeconversion. Or, during a characterization step, one may ramp thetemperature of a reaction product to detect phase transitions (meltingrange, glass transition temperature). Finally, one may maintain thereactor block at a constant temperature, while monitoring temperaturechanges in the vessels during reaction to obtain calorimetric data asdescribed below.

FIG. 6 shows a useful temperature control system 260, which comprisesseparate heating 262 and temperature sensing 264 elements. The heatingelement 262 shown in FIG. 6 is a conventional thin filament resistanceheater whose heat output is proportional to the product of the filamentresistance and the square of the current passing through the filament.The heating element 262 is shown coiled around a reactor vessel 266 toensure uniform radial and axial heating of the vessel 266 contents. Thetemperature sensing element 264 can be a TC, RTD, and the like. Theheating element 262 communicates with a processor 268, which based oninformation received from the temperature sensor 264 through atemperature monitoring system 270, increases or decreases heat output ofthe heating element 262. A heater control system 272, located in thecommunication path between the heating element 262 and the processor268, converts a processor 268 signal for an increase (decrease) inheating into an increase (decrease) in electrical current through theheating element 262. Generally, each of the vessels 104 of the parallelreactor system 100 shown in FIG. 1 or FIG. 3 are equipped with a heatingelement 262 and one or more temperature sensors 264, which communicatewith a central heater control system 272, temperature monitoring system270, and processor 268, so that the temperature of the vessels 104 canbe controlled independently.

Other embodiments include placing the heating element 262 andtemperature sensor 264 within the vessel 266, which results in moreaccurate temperature monitoring and control of the vessel 266 contents,and combining the temperature sensor and heating element in a singlepackage. A thermistor is an example of a combined temperature sensor andheater, which can be used for both temperature monitoring and controlbecause its resistance depends on temperature.

FIG. 7 illustrates another temperature control system, which includesliquid cooling and heating of the reactor block 106. Regulating thetemperature of the reactor block 106 provides many advantages. Forexample, it is a simple way of maintaining nearly uniform temperature inall of the reactor vessels 102. Because of the large surface area of thevessels 102 relative to the volume of the reaction mixture, cooling thereactor block 106 also allows one to carryout highly exothermicreactions. When accompanied by temperature control of individual vessels102, active cooling of the reactor block 106 allows for processing atsub-ambient temperatures. Moreover, active heating or cooling of thereactor block 106 combined with temperature control of individualvessels 102 or groups of vessels 102 also decreases response time of thetemperature control feedback. One may control the temperature ofindividual vessels 102 or groups of vessels 102 using compact heattransfer devices, which include electric resistance heating elements orthermoelectric devices, as shown in FIG. 6 and FIG. 8, respectively.Although we describe reactor block cooling with reference to themonolithic reactor block 106, one may, in a like manner, independentlyheat or cool individual modules 134 of the modular reactor block 132shown in FIG. 2.

Returning to FIG. 7, a thermal fluid 290, such as water, steam, asilicone fluid, a fluorocarbon, and the like, is transported from auniform temperature reservoir 292 to the reactor block 106 using aconstant or variable speed pump 294. The thermal fluid 290 enters thereactor block 106 from a pump outlet conduit 296 through an inlet port298. From the inlet port 298, the thermal fluid 290 flows through apassageway 300 formed in the reactor block 106. The passageway maycomprise single or multiple channels. The passageway 300 shown in FIG.7, consists of a single channel that winds its way between rows ofvessels 102, eventually exiting the reactor block 106 at an outlet port302. The thermal fluid 290 returns to the reservoir 292 through areactor block outlet conduit 304. A heat pump 306 regulates thetemperature of the thermal fluid 290 in the reservoir 292 by adding orremoving heat through a heat transfer coil 308. In response to signalsfrom temperature sensors (not shown) located in the reactor block 106and the reservoir 292, a processor 310 adjusts the amount of heat addedto or removed from the thermal fluid 290 through the coil 308. To adjustthe flow rate of thermal fluid 290 through the passageway 300, theprocessor 310 communicates with a valve 312 located in a reservoiroutlet conduit 314. The reactor block 106, reservoir 292, pump 294, andconduits 296, 304, 314 can be insulated to improve temperature controlin the reactor block 106.

Because the reactor block 106 is typically made of a metal or othermaterial possessing high thermal conductivity, the single channelpassageway 300 is usually sufficient for maintaining the temperature ofthe block 106 a few degrees above or below room temperature. To improvetemperature uniformity within the reactor block 106, the passageway canbe split into parallel channels (not shown) immediately downstream ofthe inlet port 298. In contrast to the single channel passageway 300depicted in FIG. 7, each of the parallel channels passes between asingle row of vessels 102 before exiting the reactor block 106. Thisparallel flow arrangement decreases the temperature gradient between theinlet 298 and outlet 302 ports. To further improve temperatureuniformity and heat exchange between the vessels 102 and the block 106,the passageway 300 can be enlarged so that the wells 104 essentiallyproject into a cavity containing the thermal fluid 290. Additionally,one may eliminate the reactor block 106 entirely, and suspend or immersethe vessels 102 in a bath containing the thermal fluid 290.

FIG. 8 illustrates the use of thermoelectric devices for heating andcooling individual vessels. Thermoelectric devices can function as bothheaters and coolers by reversing the current flow through the device.Unlike resistive heaters, which convert electric power to heat,thermoelectric devices are heat pumps that exploit the Peltier effect totransfer heat from one face of the device to the other. A typicalthermoelectric assembly has the appearance of a sandwich, in which thefront face of the thermoelectric device is in thermal contact with theobject to be cooled (heated), and the back face of the device is inthermal contact with a heat sink (source). When the heat sink or sourceis ambient air, the back face of the device typically has an array ofthermally conductive fins to increase the heat transfer area.Preferably, the heat sink or source is a liquid. Compared to air,liquids have higher thermal conductivity and heat capacity, andtherefore should provide better heat transfer through the back face ofthe device. But, because thermoelectric devices are usually made withbare metal connections, they often must be physically isolated from theliquid heat sink or source.

For example, FIG. 8 illustrates one way of using thermoelectric devices330 to heat and cool reactor vessels 338 using a liquid heat sink orsource. In the configuration shown in FIG. 8, thermoelectric devices 330are sandwiched between a reactor block 334 and a heat transfer plate336. Reactor vessels 338 sit within wells 340 formed in the reactorblock 334. Thin walls 342 at the bottom of the wells 340, separate thevessels 338 from the thermoelectric devices 330, ensuring good thermalcontact. As shown in FIG. 8, each of the vessels 338 thermally contactsa single thermoelectric device 330, although in general, athermoelectric device can heat or cool more than one of the vessels 338.The thermoelectric devices 330 either obtain heat from, or dump heatinto, a thermal fluid that circulates through an interior cavity 344 ofthe heat transfer plate 336. The thermal fluid enters and leaves theheat transfer plate 336 through inlet 346 and outlet 348 ports, and itstemperature is controlled in a manner similar to that shown in FIG. 7.During an experiment, the temperature of the thermal fluid is typicallyheld constant, while the temperature of the vessels 338 is controlled byadjusting the electrical current, and hence, the heat transport throughthe thermoelectric devices 330. Though not shown in FIG. 8, thetemperature of the vessels 338 are controlled in a manner similar to thescheme depicted in FIG. 6. Temperature sensors located adjacent to thevessels 338 and within the heat transfer plate cavity 344 communicatewith a processor via a temperature monitor. In response to temperaturedata from the temperature monitor, the processor increases or decreaseheat flow to or from the thermoelectric devices 330. A thermoelectricdevice control system, located in the communication path between thethermoelectric devices 330 and the processor, adjusts the magnitude anddirection of the flow of electrical current through each of thethermoelectric devices 330 in response to signals from the processor.

Calorimetric Data Measurement and Use

Temperature measurements often provide a qualitative picture of reactionkinetics and conversion and therefore can be used to screen librarymembers. For example, rates of change of temperature with respect totime, as well as peak temperatures reached within each of the vesselscan be used to rank catalysts. Typically, the best catalysts of anexothermic reaction are those that, when combined with a set ofreactants, result in the greatest heat production in the shortest amountof time.

In addition to its use as a screening tool, temperaturemeasurement—combined with proper thermal management and design of thereactor system—can also be used to obtain quantitative calorimetricdata. From such data, scientists can, for example, compute instantaneousconversion and reaction rate, locate phase transitions (melting point,glass transition temperature) of reaction products, or measure latentheats to deduce structural information of polymeric materials, includingdegree of crystallinity and branching.

FIG. 9 shows a cross-sectional view of a portion of a reactor block 360that can be used to obtain accurate calorimetric data. Each of thevessels 362 contain stirring blades 364 to ensure that the contents 366of the vessels 362 are well mixed and that the temperature within anyone of the vessels 362, T_(j), is uniform. Each of the vessels 362contains a thermistor 368, which measures T_(j) and heats the vesselcontents 366. The walls 370 of the vessels 362 are made of glass,although one may use any material having relatively low thermalconductivity, and similar mechanical strength and chemical resistance.The vessels 362 are held within wells 372 formed in the reactor block360, and each of the wells 372 is lined with an insulating material 374to further decrease heat transfer to or from the vessels 362. Usefulinsulating materials 374 include glass wool, silicone rubber, and thelike. The insulating material 374 can be eliminated or replaced by athermal paste when better thermal contact between that reactor block 360and the vessels 362 is desired—good thermal contact is needed, forexample, when investigating exothermic reactions under isothermalconditions. The reactor block 360 is made of a material having highthermal conductivity, such as aluminum, stainless steel, brass, and soon. High thermal conductivity, accompanied by active heating or coolingusing any of the methods described above, help maintain uniformtemperature, T_(o), throughout the reactor block 360. One can accountfor non-uniform temperatures within the reactor block 360 by measuringT_(oj), the temperature of the block 360 in the vicinity of each of thevessels 362, using block temperature sensors 376. In such cases, T_(oj),instead of T_(o), is used in the calorimetric calculations describednext.

An energy balance around the contents 366 of one of the vessels 362 (jthvessel) yields an expression for fractional conversion, X_(j), of a keyreactant at any time, t, assuming that the heat of reaction, ΔH_(rj) andthe specific heat of the vessel contents 366, C_(Pj), are known and areconstant over the temperature range of interest: $\begin{matrix}{{M_{j}c_{P,j}\frac{T_{j}}{t}} = {{m_{o,j}\Delta \quad H_{r,j}\frac{X_{j}}{t}} + Q_{{i\quad n},j} - {Q_{{out},j}.}}} & I\end{matrix}$

In expression I, M_(j) is the mass of the contents 366 of the jthvessel; m_(oj) is the initial mass of the key reactant; Q_(inj) is therate of heat transfer into the jth vessel by processes other thanreaction, as for example, by resistance heating of the thermistor 368.Q_(outj) is the rate of heat transfer out of the jth vessel, which canbe determined from the expression:

Q _(out,j) =U _(j) A _(j)(T _(j) −T _(o))=U _(j) A _(j) ΔT _(j)  II

where A_(j) is the heat transfer area—the surface area of the jthvessel—and U_(j) is the heat transfer coefficient, which depends on theproperties of the vessel 362 and its contents 366, as well as thestirring rate. U_(j) can be determined by measuring the temperaturerise, ΔT_(j), in response to a known heat input.

Equations I and II can be used to determine conversion from calorimetricdata in at least two ways. In a first method, the temperature of thereactor block 360 is held constant, and sufficient heat is added to eachof the vessels 362 through the thermistor 368 to maintain a constantvalue of ΔT_(j). Under such conditions, and after combining equations Iand II, the conversion can be calculated from the expression$\begin{matrix}{{X_{j} = {\frac{1}{m_{o,j}\Delta \quad H_{r,j}}\left( {{U_{j}A_{j}t_{j}\Delta \quad T_{j}} - {\int_{0}^{t_{f}}{Q_{{i\quad n},j}{t}}}} \right)}},} & {III}\end{matrix}$

where the integral can be determined by numerically integrating thepower consumption of the thermistor 368 over the length of theexperiment, t_(f), This method can be used to measure the heat output ofa reaction under isothermal conditions.

In a second method, the temperature of the reactor block 360 is againheld constant, but T_(j) increases or decreases in response to heatproduced or consumed in the reaction. Equation I and II become undersuch circumstances $\begin{matrix}{X_{j} = {\frac{1}{m_{o,j}\Delta \quad H_{r,j}}{\left( {{M_{j}{c_{P,j}\left( {T_{f,j} - T_{i,j}} \right)}} + {U_{j}A_{j}{\int_{0}^{t_{f}}{\Delta \quad T_{j}{t}}}}} \right).}}} & {IV}\end{matrix}$

In equation IV, the integral can be determined numerically, and T_(fj)and T_(ij) are temperatures of the reaction mixture within the jthvessel at the beginning and end of reaction, respectively.∫₀^(t_(f))Δ  T_(j)t.

Thus, if T_(fj) equals T_(tj) the total heat liberated is proportional.

This method is simpler to implement than the isothermal method since itdoes not require temperature control of individual vessels. But, it canbe used only when the temperature change in each of the reaction vessels362 due to reaction does not significantly influence the reaction understudy.

One may also calculate the instantaneous rate of disappearance of thekey reactant in the jth vessel, −r_(j), using equation I, III or IVsince −r_(j) is related to conversion through the relationship$\begin{matrix}{{{- r_{j}} = {C_{o,j}\frac{X_{j}}{t}}},} & V\end{matrix}$

which is valid for constant volume reactions. The constant C_(oj) is theinitial concentration of the key reactant.

Stirring Systems

Mixing variables such as stirring blade torque, rotation rate, andgeometry, may influence the course of a reaction and therefore affectthe properties of the reaction products. For example, the overall heattransfer coefficient and the rate of viscous dissipation within thereaction mixture may depend on the stirring blade rate of rotation.Thus, in many instances it is important that one monitor and control therate of stirring of each reaction mixture to ensure uniform mixing.Alternatively, the applied torque may be monitored in order to measurethe viscosity of the reaction mixture. As described in the next section,measurements of solution viscosity can be used to calculate the averagemolecular weight of polymeric reaction products.

FIG. 10 shows an exploded, perspective view of a stirring system for asingle module 390 of a modular reactor block of the type shown in FIG.2. The module 390 comprises a block 392 having eight wells 394 forcontaining removable reaction vessels 396. The number of wells 394 andreaction vessels 396 can vary. The top surface 398 of a removable lowerplate 400 serves as the base for each of the wells 394 and permitsremoval of the reaction vessels 396 through the bottom 402 of the block392. Screws 404 secure the lower plate 400 to the bottom 402 of theblock 392. An upper plate 406, which rests on the top 408 of the block392, supports and directs elongated stirrers 410 into the interior ofthe vessels 396. Each of the stirrers 410 comprises a spindle 412 and arotatable stirring member or stirring blade 414 which is attached to thelower end of each spindle 412. A gear 416 is attached to the upper endof each of each spindle 412. When assembled, each gear 416 meshes withan adjacent gear 416 forming a gear train (not shown) so that eachstirrer 410 rotates at the same speed. A DC stepper motor 418 providestorque for rotating the stirrers 410, although an air-driven motor, aconstant-speed AC motor, or a variable-speed AC motor can be usedinstead. A pair of driver gears 420 couple the motor 418 to the geartrain. A removable cover 422 provides access to the gear train, which issecured to the block 392 using threaded fasteners 424. In addition tothe gear train, one may employ belts, chains and sprockets, or otherdrive mechanisms. In alternate embodiments, each of the stirrers 410 arecoupled to separate motors so that the speed or torque of each of thestirrers 410 can be independently varied and monitored. Furthermore, thedrive mechanism—whether employing a single motor and gear train orindividual motors—can be mounted below the vessels 362. In such cases,magnetic stirring blades placed in the vessels 362 are coupled to thedrive mechanism using permanent magnets attached to gear train spindlesor motor shafts.

In addition to the stirring system, other elements shown in FIG. 10merit discussion. For example, the upper plate 406 may contain vesselseals 426 that allow processing at pressures different than atmosphericpressure. Moreover, the seals 426 permit one to monitor pressure in thevessels 396 over time. As discussed below, such information can be usedto calculate conversion of a gaseous reactant to a condensed species.Note that each spindle 412 may penetrate the seals 426, or may bemagnetically coupled to an upper spindle member (not shown) attached tothe gear 416. FIG. 10 also shows temperature sensors 428 embedded in theblock 392 adjacent to each of the wells 394. The sensors 428 are part ofthe temperature monitoring and control system described previously.

In another embodiment, an array of electromagnets rotate freestandingstirring members or magnetic stirring bars, which obviates the need forthe mechanical drive system shown in FIG. 10. Electromagnets areelectrical conductors that produce a magnetic field when an electriccurrent passes through them. Typically, the electrical conductor is awire coil wrapped around a solid core made of material having relativelyhigh permeability, such as soft iron or mild steel.

FIG. 11 is a schematic representation of one embodiment of anelectromagnet stirring array 440. The electromagnets 442 or coilsbelonging to the array 440 are mounted in the lower plate 400 of thereactor module 390 of FIG. 10 so that their axes are about parallel tothe centerlines of the vessels 396. Although greater magnetic fieldstrength can be achieved by mounting the electromagnets with their axesperpendicular to the centerlines of the vessels 396, such a design ismore difficult to implement since it requires placing electromagnetsbetween the vessels 396. The eight crosses or vessel sites 444 in FIG.11 mark the approximate locations of the respective centers of each ofthe vessels 396 of FIG. 10 and denote the approximate position of therotation axes of the magnetic stirring bars (not shown). In the array440 shown in FIG. 11, four electromagnets 442 surround each vessel site444, though one may use fewer or greater numbers of electromagnets 442.The minimum number of electromagnets per vessel site is two, but in sucha system it is difficult to initiate stirring, and it is common to stallthe stirring bar. Electromagnet size and available packing densityprimarily limit the maximum number of electromagnets.

As illustrated in FIG. 11, each vessel site 444, except those at theends 446 of the array 440, shares its four electromagnets 442 with twoadjacent vessel sites. Because of this sharing, magnetic stirring barsat adjacent vessel sites rotate in opposite directions, as indicated bythe curved arrows 448 in FIG. 11, which may lead to stalling. Otherarray configurations are possible. For example, FIG. 12 shows a portionof an array 460 in which the ratio of electromagnets 462 to vessel sites464 approaches 1:1 as the number of vessel sites 464 becomes large.Because each of the vessel sites 464 shares its electromagnets 462 withits neighbors, magnetic stirring bars at adjacent vessel sites rotate inopposite directions, as shown by curved arrows 466. In contrast, FIG. 13shows a portion of an array 470 in which the ratio of electromagnets 472to vessel sites 474 approaches 2:1 as the number of vessel sites becomeslarge. Because of the comparatively large number of electromagnets 472to vessel sites 474, all of the magnetic stirring bars can be made torotate in the same direction 476, which minimizes stalling. Similarly,FIG. 14 shows an array 480 in which the number of electromagnets 482 tovessel sites 484 is 4:1. Each magnetic stirring bar rotates in the samedirection 486.

FIG. 15 illustrates additional elements of an electromagnetic stirringsystem 500. For clarity, FIG. 15 shows a square electromagnet array 502comprised of four electromagnets 504, although larger arrays, such asthose shown in FIGS. 12-14, can be used. Each of the electromagnets 504comprises a wire 506 wrapped around a high permeability solid core 508.The pairs of electromagnets 504 located on the two diagonals of thesquare array 502 are connected in series to form a first circuit 510 anda second circuit 512. The first 510 and second 512 circuits areconnected to a drive circuit 514, which is controlled by a processor516. Electrical current, whether pulsed or sinusoidal, can be variedindependently in the two circuits 510, 512 by the drive circuit 514 andprocessor 516. Note that within each circuit 510, 512, the current flowsin opposite directions in the wire 506 around the core 508. In this way,each of the electromagnets 504 within a particular circuit 510, 512 haveopposite magnetic polarities. The axes 518 of the electromagnets 504 areabout parallel to the centerline 520 of the reactor vessel 522. Amagnetic stirring bar 524 rests on the bottom of the vessel 522 prior tooperation. Although the electromagnets 504 can also be oriented withtheir axes 518 perpendicular to the vessel centerline 520, the parallelalignment provides higher packing density.

FIG. 16 shows the magnetic field direction of a 2×2 electromagnet arrayat four different times during one full rotation of the magneticstirring bar 524 of FIG. 15, which is rotating at a steady frequency ofω radians s⁻¹. In FIG. 16, a circle with a plus sign 532 indicates thatthe electromagnet produces a magnetic field in a first direction; acircle with a minus sign 534 indicates that the electromagnet produces amagnetic field in a direction opposite to the first direction; and acircle with no sign 536 indicates that the electromagnet produces nomagnetic field. At time t=0, the electromagnets 530 produce an overallmagnetic field with a direction represented by a first arrow 538 at thevessel site. At time ${t = \frac{\pi}{2\omega}},$

the electromagnets 540 produce an overall magnetic field with adirection represented by a second arrow 542. Since the magnetic stirringbar 524 (FIG. 15) attempts to align itself with the direction of theoverall magnetic field, it rotates clockwise ninety degrees from thefirst direction 538 to the second direction 542. At time${t = \frac{\pi}{\omega}},$

the electromagnets 544 produce an overall magnetic field with adirection represented by a third arrow 546. Again, the magnetic stirringbar 524 aligns itself with the direction of the overall magnetic field,and rotates clockwise an additional ninety degrees. At time${t = \frac{3\pi}{2\omega}},$

the electromagnets 548 produce an overall magnetic field with adirection represented by a fourth arrow 550, which rotates the magneticstirring bar 524 clockwise another ninety degrees. Finally, at time${t = \frac{2\pi}{\omega}},$

the electromagnets 530 produce an overall magnetic field with directionrepresented by the first arrow 538, which rotates the magnetic stirringbar 524 back to its position at time t=0.

FIG. 17 illustrates magnetic field direction of a 4×4 electromagneticarray at five different times during one full rotation of a 3×3 array ofmagnetic stirring bars. As in FIG. 15, a circle with a plus sign 570, aminus sign 572, or no sign 574 represents the magnetic field directionof an individual electromagnet, while an arrow 576 represents thedirection of the overall magnetic field at a vessel site. As shown,sixteen electromagnets are needed to rotate nine magnetic stirring bars.But, as indicated in FIG. 18, due to sharing of electromagnets bymultiple magnetic stirring bars, the rotational direction of themagnetic fields is non-uniform. Thus, five of the fields rotate in aclockwise direction 590 while the remaining four fields rotate in acounter-clockwise direction 592.

FIG. 19 and FIG. 20 illustrate wiring configurations for electromagnetarrays in which each vessel site is located between four electromagnetsdefining four corners of a quadrilateral sub-array. For each vesselsite, both wiring configurations result in an electrical connectionbetween electromagnets located on the diagonals of a given sub-array. Inthe wiring configuration 610 shown in FIG. 19, electromagnets 612 inalternating diagonal rows are wired together to form two series ofelectromagnets 612. Dashed and solid lines represent electricalconnections between electromagnets 612 in a first series 614 and asecond series 616, respectively. Plus signs 618 and minus signs 620indicate polarity (magnetic field direction) of individualelectromagnets 612 at any time, t, when current in the first series 614and the second series 616 of electromagnets 612 are in phase. FIG. 20illustrates an alternate wiring configuration 630 of electromagnets 632,where again, dashed and solid lines represent electrical connectionsbetween the first 634 and second series 636 of electromagnets 632, andplus signs 638 and minus signs 640 indicate magnetic polarity.

Note that for both wiring configurations 610, 630, the polarities of theelectromagnets 612, 632 of the first series 614, 634 are not the same,though amplitudes of the current passing through the connections betweenthe electromagnets 612, 632 of the first series 614, 634 are equivalent.The same is true for the second series 616, 636 of electromagnets 612,632. One can achieve opposite polarities within the first series 614,634 or second series 616, 636 of electromagnets 612, 632 by reversingthe direction of electrical current around the core of the electromagnet612, 632. See, for example, FIG. 15. In the two wiring configurations610, 630 of FIGS. 19 and 20, every quadrilateral array of four adjacentelectromagnets 612, 632 defines a site for rotating a magnetic stirringbar, and the diagonal members of each of the four adjacentelectromagnets 612, 632 belong to the first series 614, 634 and thesecond 616, 636 series of electromagnets 612, 632. Moreover, within anyset of four adjacent electromagnets 612, 632, each pair ofelectromagnets 612, 632 belonging to the same series have oppositepolarities. The two wiring configurations 610, 630 of FIGS. 19 and 20can be used with any of the arrays 460, 470, 480 shown in FIGS. 12-14.

The complex wiring configurations 610, 630 of FIGS. 19 and 20 can beplaced on a printed circuit board, which serves as both a mechanicalsupport and alignment fixture for the electromagnets 612, 632. The useof a printed circuit board allows for rapid interconnection of theelectromagnets 612, 632, greatly reducing assembly time and cost, andeliminating wiring errors associated with manual soldering of hundredsof individual connections. Switches can be used to turn stirring on andoff for individual rows of vessels. A separate drive circuit may be usedfor each row of vessels, which allows stirring speed to be used as avariable during an experiment.

FIG. 21 is a plot 650 of current versus time and shows the phaserelationship between sinusoidal source currents, I_(A)(t) 652 andI_(B)(t) 654, which drive, respectively, the first series 614, 634 andthe second series 616, 636 of electromagnets 612, 632 shown in FIGS. 19and 20. The two source currents 652, 654 have equivalent peak amplitudeand frequency, ω_(D), though I_(A)(t) 652 lags I_(B)(t) 654 by {fraction(π/2)} radians. Because of this phase relationship, magnetic stirringbars placed at rotation sites defined by any four adjacentelectromagnets 612, 632 of FIGS. 19 and 20 will each rotate at anangular frequency of ω_(D), though adjacent stirring bars will rotate inopposite directions when the electromagnet array 460 depicted in FIG. 12is used. If, however, the arrays 470, 480 shown in FIGS. 13 and 14 areused, adjacent stirring bars will rotate in the same direction. In analternate embodiment, a digital approximation to a sine wave can beused.

FIG. 22 is a block diagram of a power supply 670 for an electromagnetarray 672. Individual electromagnets 674 are wired together in a firstand second series as, for example, shown in FIG. 19 or 20. The first andsecond series of electromagnets 674 are connected to a power source 676,which provides the two series with sinusoidal driving currents that are{fraction (π/2)} radians out of phase. Normally, the amplitudes of thetwo driving currents are the same and do not depend on frequency. Aprocessor 678 controls both the amplitude and the frequency of thedriving currents.

Viscosity and Related Measurements

The present invention provides for in situ measurement of viscosity andrelated properties. As discussed below, such data can be used, forexample, to monitor reactant conversion, and to rank or characterizematerials based on molecular weight or particle size.

The viscosity of a polymer solution depends on the molecular weight ofthe polymer and its concentration in solution. For polymerconcentrations well below the “semidilute limit”—the concentration atwhich the solvated polymers begin to overlap one another—the solutionviscosity, η, is related to the polymer concentration, C, in the limitas C approaches zero by the expression

η=(1+C[η])η_(S)  VI

where η, is the viscosity of the solvent. Essentially, adding polymer toa solvent increases the solvent's viscosity by an amount proportional tothe polymer concentration. The proportionality constant [72 ], is knownas the intrinsic viscosity, and is related to the polymer molecularweight, M, through the expression

[η]=[η₀ ]M ^(α),  VII

where [η₀] and α are empirical constants. Equation VII is known as theMark-Houwink-Sakurda (MHS) relation, and it, along with equation VI, canbe used to determine molecular weight from viscosity measurements.

Equation VI requires concentration data from another source; withpolymerization reactions, polymer concentration is directly related tomonomer conversion. In the present invention, such data can be obtainedby measuring heat evolved during reaction (see equation III and IV) or,as described below, by measuring the amount of a gaseous reactantconsumed during reaction. The constants in the MHS relation arefunctions of temperature, polymer composition, polymer conformation, andthe quality of the polymer-solvent interaction. The empirical constants,[η₀] and α, have been measured for a variety of polymer-solvent pairs,and are tabulated in the literature.

Although equations VI and VII can be used to approximate molecularweight, in situ measurements of viscosity in the present invention areused mainly to rank reaction products as a function of molecular weight.Under most circumstances, the amount of solvent necessary to satisfy theconcentration requirement of equation VI would slow the rate of reactionto an unacceptable level. Therefore, most polymerizations are carriedout at polymer concentrations above the semidilute limit, where the useof equations VI and VII to calculate molecular weight would lead tolarge error. Nevertheless, viscosity can be used to rank reactionproducts even at concentrations above the semidilute limit since a risein viscosity during reaction generally reflects an increase in polymerconcentration, molecular weight or both. If necessary, one canaccurately determine molecular weight from viscosity measurements atrelatively high polymer concentration by first preparingtemperature-dependent calibration curves that relate viscosity tomolecular weight. But the curves would have to be obtained for everypolymer-solvent pair produced, which weighs against their use forscreening new polymeric materials.

In addition to ranking reactions, viscosity measurements can also beused to screen or characterize dilute suspensions of insolubleparticles—polymer emulsions or porous supports for heterogeneouscatalysts—in which viscosity increases with particle size at a fixednumber concentration. In the case of polymer emulsions, viscosity canserve as a measure of emulsion quality. For example, solution viscositythat is constant over long periods of time may indicate superioremulsion stability, or viscosity within a particular range may correlatewith a desired emulsion particle size. With porous supports, viscositymeasurements can be used to identify active catalysts: in many cases,the catalyst support will swell during reaction due to the formation ofinsoluble products within the porous support.

In accordance with the present invention, viscosity or relatedproperties of the reactant mixtures are monitored by measuring theeffect of viscous forces on stirring blade rotation. Viscosity is ameasure of a fluid's resistance to a shear force. This shear force isequal to the applied torque, Γ; needed to maintain a constant angularvelocity of the stirring blade. The relationship between the viscosityof the reaction mixture and the applied torque can be expressed as

Γ=K _(ω)(ω,T)η  VIII

where K_(ω), is a proportionality constant that depends on the angularfrequency, ω, of the stirring bar, the temperature of the reactionmixture, and the geometries of the reaction vessel and the stirringblade. K_(ω) can be obtained through calibration with solutions of knownviscosity.

During a polymerization, the viscosity of the reaction mixture increasesover time due to the increase in molecular weight of the reactionproduct or polymer concentration or both. This change in viscosity canbe monitored by measuring the applied torque and using equation VIII toconvert the measured data to viscosity. In many instances, actual valuesfor the viscosity are unnecessary, and one can dispense with theconversion step. For example, in situ measurements of applied torque canbe used to rank reaction products based on molecular weight orconversion, as long as stirring rate, temperature, vessel geometry andstirring blade geometry are about the same for each reaction mixture.

FIG. 23 illustrates an apparatus 700 for directly measuring the appliedtorque. The apparatus 700 comprises a stirring blade 702 coupled to adrive motor 704 via a rigid drive spindle 706. The stirring blade 702 isimmersed in a reaction mixture 708 contained within a reactor vessel710. Upper 712 and lower 714 supports prevent the drive motor 704 andvessel 710 from rotating during operation of the stirring blade 702. Forsimplicity, the lower support 714 can be a permanent magnet. A torque orstrain gauge 716 shown mounted between the upper support 712 and thedrive motor 704 measures the average torque exerted by the motor 704 onthe stirring blade 702. In alternate embodiments, the strain gauge 716is inserted within the drive spindle 706 or is placed between the vessel710 and the lower support 714. If located within the drive spindle 706,a system of brushes or commutators (not shown) are provided to allowcommunication with the rotating strain gauge. Often, placement of thestrain gauge 716 between the vessel 710 and the lower support 714 is thebest option since many stirring systems, such as the one shown in FIG.10, use a single motor to drive multiple stirring blades.

FIG. 24 shows placement of a strain gauge 730 in a portion of a baseplate 732 that is similar to the lower plate 400 of the reactor module390 shown in FIG. 10. The lower end 734 of the strain gauge 730 isrigidly attached to the base plate 732. A first permanent magnet 736 ismounted on the top end 738 of the strain gauge 730, and a secondpermanent magnet 740 is attached to the bottom 742 of a reactor vessel744. When the vessel 744 is inserted in the base plate 732, the magneticcoupling between the first magnet 736 and the second magnet 740 preventsthe vessel 744 from rotating and transmits torque to the strain gauge730.

Besides using a strain gauge, one can also monitor drive motor powerconsumption, which is related to the applied torque. Referring again toFIG. 23, the method requires monitoring and control of the stirringblade 702 rotational speed, which can be accomplished by mounting asensor 718 adjacent to the drive spindle 706. Suitable sensors 718include optical detectors, which register the passage of a spot on thedrive spindle 706 by a reflectance measurement, or which note theinterruption of a light beam by an obstruction mounted on the drivespindle 706, or which discern the passage of a light beam through a sloton the drive spindle 706 or on a co-rotating obstruction. Other suitablesensors 718 include magnetic field detectors that sense the rotation ofa permanent magnet affixed to the spindle 706. Operational details ofmagnetic field sensors are described below in the discussion of phaselag detection. Sensors such as encoders, resolvers, Hall effect sensors,and the like, are commonly integrated into the motor 704. An externalprocessor 720 adjusts the power supplied to the drive motor 704 tomaintain a constant spindle 706 rotational speed. By calibrating therequired power against a series of liquids of known viscosity, theviscosity of an unknown reaction mixture can be determined.

In addition to direct measurement, torque can be determined indirectlyby measuring the phase angle or phase lag between the stirring blade andthe driving force or torque. Indirect measurement requires that thecoupling between the driving torque and the stirring blade is “soft,” sothat significant and measurable phase lag occurs.

With magnetic stirring, “soft” coupling occurs automatically. The torqueon the stirring bar is related to the magnetic moment of the stirringbar, μ, and the amplitude of the magnetic field that drives the rotationof the stirring bar, H, through the expression

Γ=μH sin θ,  IX

where θ is the angle between the axis of the stirring bar (magneticmoment) and the direction of the magnetic field. At a given angularfrequency, and for known μ and H, the phase angle, θ, will automaticallyadjust itself to the value necessary to provide the amount of torqueneeded at that frequency. If the torque required to stir at frequency ωis proportional to the solution viscosity and the stirring frequency-anapproximation useful for discussion—then the viscosity can be calculatedfrom measurements of the phase angle using the equation

Γ=μH sin θ=αηω  X

where α is a proportionality constant that depends on temperature, andthe geometry of the vessel and the stirring blade. In practice, one mayuse equation VIII or a similar empirical expression for the right handside of equation X if the torque does not depend linearly on theviscosity-frequency product.

FIG. 25 shows an inductive sensing coil system 760 for measuring phaseangle or phase lag, θ. The system 760 comprises four electromagnets 762,which drive the magnetic stirring bar 764, and a phase-sensitivedetector, such as a standard lock-in amplifier (not shown). A gradientcoil 766 configuration is used to sense motion of the stirring bar 764,though many other well known inductive sensing coil configurations canbe used. The gradient coil 766 is comprised of a first sensing coil 768and a second sensing coil 770 that are connected in series and arewrapped in opposite directions around a first electromagnet 772. Becauseof their opposite polarities, any difference in voltages induced in thetwo sensing coils 768, 770 will appear as a voltage difference acrossthe terminals 774, which is detected by the lock-in amplifier. If nostirring bar 764 is present, then the alternating magnetic field of thefirst electromagnet 772 will induce approximately equal voltages in eachof the two coils 768, 770—assuming they are mounted symmetrically withrespect to the first electromagnet 772—and the net voltage across theterminals 774 will be about zero. When a magnetic stirring bar 764 ispresent, the motion of the rotating magnet 764 will induce a voltage ineach of the two sensing coils 768, 770. But, the voltage induced in thefirst coil 768, which is closer to the stirring bar 764, will be muchlarger than the voltage induced in the second coil 770, so that thevoltage across the terminals 774 will be nonzero. A periodic signal willthus be induced in the sensing coils 768, 770, which is measured by thelock-in amplifier.

FIG. 26 and FIG. 27 show typical outputs 790, 810 from the inductivesensing coil system 760 of FIG. 25, which illustrate phase lagassociated with magnetic stirring for low and high viscosity solutions,respectively. Periodic signals 792, 812 from the sensing coils 768, 770are plotted with sinusoidal reference signals 794, 814 used to drive theelectromagnets. Time delay, Δt 796, 816, between the periodic signals792, 812 and the reference signals 794, 814 is related to the phaseangle by θ=ω·Δt. Visually comparing the two outputs 790, 810 indicatesthat the phase angle associated with the high viscosity solution islarger than the phase angle associated with the low viscosity solution.

FIG. 27 illustrates how amplitude and phase angle will vary during areaction as the viscosity increases from a low value to a valuesufficient to stall the stirring bar. A waveform or signal 820 from thesensing coils is input to a lock-in amplifier 822, using the drivecircuit sinusoidal current as a phase and frequency reference signal824. The lock-in amplifier 822 outputs the amplitude 826 of the sensingcoil signal 820, and phase angle 828 or phase lag relative to thereference signal 824. The maximum phase angle is {fraction (π/2)}radians, since, as shown by equation X, torque decreases with furtherincreases in θ leading to slip of the stirring bar 764 of FIG. 25. Thus,as viscosity increases during reaction, the phase angle 828 or phase lagalso increases until the stirring bar stalls, and the amplitude 826abruptly drops to zero. This can be seen graphically in FIG. 27, whichshows plots of {overscore (A)} 830 and {overscore (θ)} 832, theamplitude of the reference signal and phase angle, respectively,averaged over many stirring bar rotations. One can optimize thesensitivity of the phase angle 828 measurement by proper choice of themagnetic field amplitude and frequency.

To minimize interference from neighboring stirring bars—ideally, eachset of gradient coils should sense the motion of a single stirringbar—each vessel should be provided with electromagnets that are notshared with adjacent vessels. For example, a 4:1 magnet array shown inFIG. 14 should be used instead of the 2:1 or the 1:1 magnet arrays shownin FIGS. 13 and 12, respectively. In order to take readings from all ofthe vessels in an array, a multiplexer can be used to sequentially routesignals from each vessel to the lock-in amplifier. Normally, an accuratemeasurement of the phase angle can be obtained after several tens ofrotations of the stirring bars. For rotation frequencies of 10-20 Hz,this time will be on the order of a few seconds per vessel. Thus, phaseangle measurements for an entire array of vessels can be typically madeonce every few minutes, depending on the number of vessels, the stirringbar frequency, and the desired accuracy. In order to speed up themeasurement process, one may employ multiple-channel signal detection tomeasure the phase angle of stirring bars in more than one vessel at atime. Alternate detection methods include direct digitization of thecoil output waveforms using a high-speed multiplexer and/or ananalog-to-digital converter, followed by analysis of stored waveforms todetermine amplitude and phase angle.

Phase angle measurements can also be made with non-magnetic, mechanicalstirring drives, using the inductive coil system 760 of FIG. 25. Forexample, one may achieve sufficient phase lag between the stirring bladeand the drive motor by joining them with a torsionally soft, flexibleconnector. Alternatively, the drive mechanism may use a resilient beltdrive rather than a rigid gear drive to produce measurable phase lag.The stirring blade must include a permanent magnet oriented such thatits magnetic moment is not parallel to the axis of rotation. For maximumsensitivity, the magnetic moment of the stirring blade should lie in theplane of rotation. Note that one advantage to using a non-magneticstirring drive is that there is no upper limit on the phase angle.

In addition to directly or indirectly measuring torque, one may senseviscosity by increasing the driving frequency, ω_(D), or decreasing themagnetic field strength until, in either case, the stirring bar stallsbecause of insufficient torque. The point at which the stirring barstops rotating can be detected using the same setup depicted in FIG. 25for measuring phase angle. During a ramp up (down) of the drivingfrequency (field strength), the magnitude of the lock-in amplifieroutput will abruptly fall by a large amount when the stirring barstalls. The frequency or field strength at which the stirring bar stallscan be correlated with viscosity: the lower the frequency or the higherthe field strength at which stalling occurs, the greater the viscosityof the reaction mixture.

With appropriate calibration, the method can yield absolute viscositydata, but generally the method is used to rank reactions. For example,when screening multiple reaction mixtures, one may subject all of thevessels to a series of step changes in either frequency or fieldstrength, while noting which stirring bars stall after each of the stepchanges. The order in which the stirring bars stall indicates therelative viscosity of the reaction mixtures since stirring bars immersedin mixtures having higher viscosity will stall early. Note that, inaddition to providing data on torque and stall frequency, the inductivesensing coil system 760 of FIG. 25 and similar devices can be used asdiagnostic tools to indicate whether a magnetic stirring bar has stoppedrotating during a reaction.

Mechanical Oscillators

Piezoelectric quartz resonators or mechanical oscillators can be used toevaluate the viscosity of reaction mixtures, as well as a host of othermaterial properties, including molecular weight, specific gravity,elasticity, dielectric constant, and conductivity. In a typicalapplication, the mechanical oscillator, which can be as small as a fewmm in length, is immersed in the reaction mixture. The response of theoscillator to an excitation signal is obtained for a range of inputsignal frequencies, and depends on the composition and properties of thereaction mixture. By calibrating the resonator with a set of wellcharacterized liquid standards, the properties of the reaction mixturecan be determined from the response of the mechanical oscillator.Further details on the use of piezoelectric quartz oscillators tomeasure material properties are described in co-pending U.S. patentapplication Ser. No 09/133,171 “Method and Apparatus for CharacterizingMaterials by Using a Mechanical Resonator,” filed Aug. 12, 1998, whichis herein incorporated by reference.

Although many different kinds of mechanical oscillators currently exist,some are less useful for measuring properties of liquid solutions. Forexample, ultrasonic transducers or oscillators cannot be used in allliquids due to diffraction effects and steady acoustic (compressive)waves generated within the reactor vessel. These effects usually occurwhen the size of the oscillator and the vessel are not much greater thanthe characteristic wavelength of the acoustic waves. Thus, for reactorvessel diameters on the order of a few centimeters, the frequency of themechanical oscillator should be above 1 MHz. Unfortunately, complexliquids and mixtures, including polymer solutions, often behave likeelastic gels at these high frequencies, which results in inaccurateresonator response.

Often, shear-mode transducers as well as various surface-wavetransducers can be used to avoid some of the problems associated withtypical ultrasonic transducers. Because of the manner in which theyvibrate, shear mode transducers generate viscous shear waves instead ofacoustic waves. Since viscous shear waves decay exponentially withdistance from the sensor surface, such sensors tend to be insensitive tothe geometry of the measurement volume, thus eliminating mostdiffraction and reflection problems. Unfortunately, the operatingfrequency of these sensors is also high, which, as mentioned above,restricts their use to simple fluids. Moreover, at high vibrationfrequencies, most of the interaction between the sensor and the fluid isconfined to a thin layer of liquid near the sensor surface. Anymodification of the sensor surface through adsorption of solutioncomponents will often result in dramatic changes in the resonatorresponse.

Tuning forks 840 and bimorph/unimorph resonators 850 shown in FIG. 28and FIG. 29, respectively, overcome many of the drawbacks associatedwith ultrasonic transducers. Because of their small size, tuning forks840 and bimorph/unimorph resonators 850 have difficulty excitingacoustic waves, which typically have wavelengths many times their size.Furthermnore, though one might conclude otherwise based on the vibrationmode shown in FIG. 28, tuning forks 840 generate virtually no acousticwaves: when excited, each of the tines 832 of the tuning fork 840 actsas a separate acoustic wave generator, but because the tines 832oscillate in opposite directions and phases, the waves generated by eachof the tines 832 cancel one another. Like the shear mode transducersdescribed above, the bimorph/unimorph 850 resonators producepredominantly viscous waves and therefore tend to be insensitive to thegeometry of the measurement volume. But unlike the shear modetransducers, bimorph/unimorph 850 resonators operate at much lowerfrequencies, and therefore can be used to measure properties ofpolymeric solutions.

FIG. 30 schematically shows a system 870 for measuring the properties ofreaction mixtures using mechanical oscillators 872. An importantadvantage of the system 870 is that it can be used to monitor theprogress of a reaction. The oscillators 872 are mounted on the interiorwalls 874 of the reaction vessels 876. Alternatively, the oscillators872 can be mounted along the bottom 878 of the vessels 876 or can befreestanding within the reaction mixtures 880. Each oscillator 872communicates with a network analyzer 882 (for example, an HP8751Aanalyzer), which generates a variable frequency excitation signal. Eachof the oscillators 872 also serve as receivers, transmitting theirresponse signals back to the network analyzer 882 for processing. Thenetwork analyzer 882 records the responses of the oscillators 872 asfunctions of frequency, and sends the data to storage 884. The outputsignals of the oscillators 872 pass through a high impedance bufferamplifier 886 prior to measurement by the wide band receiver 888 of thenetwork analyzer 882.

Other resonator designs may be used. For example, to improve thesuppression of acoustic waves, a tuning fork resonator with four tinescan be used. It is also possible to excite resonator oscillationsthrough the use of voltage spikes instead of a frequency sweeping ACsource. With voltage spike excitation, decaying free oscillations of theresonator are recorded instead of the frequency response. A variety ofsignal processing techniques well known to those of skill in the art canbe used to distinguish resonator responses.

Alternate embodiments can be described with reference to the parallelreactor system 130 shown in FIG. 2. A single resonator (not shown) isattached to the 3-axis translation system 150. The translation system150, at the direction of the processor 160, places the resonator withina reactor vessel of interest. A reading of resonator response is takenand compared to calibration curves, which relate the response toviscosity, molecular weight, specific gravity, or other properties. Inanother embodiment, a portion of the reaction mixture is withdrawn froma reactor vessel, using, for example, the liquid handling system 146,and is placed in a separate vessel containing a resonator. The responseof the resonator is measured and compared to calibration data. Althoughthe system 870 shown in FIG. 30 is better suited to monitor solutionproperties in situ, the two alternate embodiments can be used aspost-characterization tools and are much simpler to implement.

In addition to mechanical oscillators, other types of sensors can beused to evaluate material properties. For example, interdigitatedelectrodes can be used to measure dielectric properties of the reactionmixtures.

Pressure Control System

Another technique for assessing reaction kinetics is to monitor pressurechanges due to production or consumption of various gases duringreaction. One embodiment of this technique is shown in FIG. 31. Aparallel reactor 910 comprises a group of reactor vessels 912. Agas-tight cap 914 seals each of the vessels 912 and preventsunintentional gas flow to or from the vessels 912. Prior to placement ofthe cap 914, each of the vessels 912 is loaded with liquid reactants,solvents, catalysts, and other condensed-phase reaction components usingthe liquid handling system 146 shown in FIG. 2. Gaseous reactants fromsource 916 are introduced into each of the vessels 912 through a gasinlet 918. Valves 920, which communicate with a controller 922, are usedto fill the reaction vessels 912 with the requisite amount of gaseousreactants prior to reaction. A pressure sensor 924 communicates with thevessel head space—the volume within each of the vessels 912 thatseparates the cap 914 from the liquid components—through a port 926located in the cap 914. The pressure sensors 924 are coupled to aprocessor 928, which manipulates and stores data. During reaction, anychanges in the head space pressure, at constant temperature, reflectchanges in the amount of gas present in the head space. This pressuredata can be used to determine the molar production or consumption rate,r_(j), of a gaseous component since, for an ideal gas at constanttemperature, $\begin{matrix}{r_{i} = {\frac{1}{RT}\frac{p_{i}}{t}}} & {XI}\end{matrix}$

where R is the universal gas constant and p_(i) is the partial pressureof the ith gaseous component. Temperature sensors 930, which communicatewith the processor 928 through monitor 932, provide data that can beused to account for changes in pressure resulting from variations inhead space temperature. The ideal gas law or similar equation of statecan be used to calculate the pressure correction.

In an alternate embodiment, the valves 920 are used to compensate forthe consumption of a gaseous reactant, in a reaction where there is anet loss in moles of gas-phase components. The valves 920 are regulatedby the valve controller 922, which communicates with the processor 928.At the beginning of the reaction, the valves 920 open to allow gas fromthe high pressure source 916 to enter each of the vessels 912. Once thepressure within each of the vessels 912, as read by the sensor 924,reaches a predetermined value, P_(H), the processor 928 closes thevalves 920. As the reaction consumes the source 916 gas, the totalpressure within each of the vessels 912 decreases. Once the pressure ina particular vessel 912 falls below a predetermined value, P_(L), theprocessor 928 opens the valve 920 associated with the particular vessel912, repressurizing it to P_(H). This process—filling each of thevessels 912 with source 916 gas to P_(H), allowing the head spacepressure to drop below P_(L), and then refilling the vessels 912 withsource 916 gas to P_(H)—is usually repeated many times during the courseof the reaction. Furthermore, the total pressure in the head space ofeach of the vessels 912 is continuously monitored and recorded duringthe gas fill-pressure decay cycle.

An analogous method can be used to investigate reactions where there isa net gain of gas-phase components. At the beginning of a reaction, allreaction materials are introduced into the vessels 912 and the valves920 are closed. As the reaction proceeds, gas production results in arise in head space pressure, which sensors 924 and processor 928 monitorand record. Once the pressure within a particular vessel 912 reachesP_(H), the processor 928 directs the controller 922 to open theappropriate valve 920 to depressurize the vessel 912. The valve 920,which is a multi-port valve, vents the gas from the head space throughan exhaust line 934. Once the head space pressure falls below P_(L), theprocessor 928 instructs the controller 922 to close the valve 920. Thetotal pressure is continuously monitored and recorded during the gasrise-vent cycle.

The gas consumption (production) rates can be estimated from the totalpressure data by a variety of methods. For simplicity, these methods aredescribed in terms of a single reactor vessel 912 and valve 920, butthey apply equally well to a parallel reactor 910 comprising multiplevessels 912 and valves 920. One estimate of gas consumption (production)can be made from the slope of the pressure decay (growth) curvesobtained when the valve is closed. These data, after converting totalpressure to partial pressure based on reaction stoichiometry, can beinserted into equation XI to calculate r_(i), the molar consumption(production) rate. A second estimate can be made by assuming that afixed quantity of gas enters (exits) the vessel during each valve cycle.The frequency at which the reactor is repressurized (depressurized) istherefore proportional to the gas consumption (production) rate. Athird, more accurate estimate can be obtained by assuming a known gasflow rate through the valve. Multiplying this value by the time duringwhich the valve remains open yields an estimate for the quantity of gasthat enters or leaves the vessel during a particular cycle. Dividingthis product by the time between the next valve cycle—that is, the timeit takes for the pressure in the vessel head space to fall from P_(H) toP_(L)—yields an average value for the volumetric gas consumption(production) rate for the particular valve cycle. Summing the quantityof gas added during all of the cycles equals the total volume of gasconsumed (produced) during the reaction.

The most accurate results are obtained by directly measuring thequantity of gas that flows through the valve. This can be done by notingthe change in pressure that occurs during the time the valve is open-theideal gas law can be used to convert this change to the volume of gasthat enters or leaves the vessel. Dividing this quantity by the timebetween a particular valve cycle yields an average volumetric gasconsumption (production) rate for that cycle. Summing the volume changesfor each cycle yields the total volume of gas consumed (produced) in thereaction.

In an alternate embodiment shown in FIG. 31, the gas consumption rate isdirectly measured by inserting flow sensors 936 downstream of the valves920 or by replacing the valves 920 with flow sensors 936. The flowsensors 936 allow continuous monitoring of the mass flow rate of gasentering each of the vessels 912 through the gas inlet 918. To ensuremeaningful comparisons between experiments, the pressure of the source916 gas should remain about constant during an experiment. Although theflow sensors 936 eliminate the need for cycling the valves 920, theminimum detectable flow rates of this embodiment are less than thoseemploying pressure cycling. But, the use of flow sensors 936 isgenerally preferred for fast reactions where the reactant flow ratesinto the vessels 912 are greater than the threshold sensitivity of theflow sensors 936.

Illustrative Example of Calibration of Mechanical Oscillators forMeasuring Molecular Weight

Mechanical oscillators were used to characterize reaction mixturescomprising polystyrene and toluene. To relate resonator response to themolecular weight of polystyrene, the system 870 illustrated in FIG. 30was calibrated using polystyrene standards of known molecular weightdissolved in toluene. Each of the standard polystyrene-toluene solutionshad the same concentration, and were run in separate (identical) vesselsusing tuning fork piezoelectric quartz resonators similar to the oneshown in FIG. 28. Frequency response curves for each resonator wererecorded at intervals between about 10 and 30 seconds.

The calibration runs produced a set of resonator responses that could beused to relate the output from the oscillators 872 immersed in reactionmixtures to polystyrene molecular weight. FIG. 32 shows results ofcalibration runs 970 for the polystyrene-toluene solutions. The curvesare plots of oscillator response for polystyrene-toluene solutionscomprising no polystyrene 952, and polystyrene standards having weightaverage molecular weights (M_(W)) of 2.36×10³ 954, 13.7×10³ 956,114.2×10³ 958, and 1.88×10⁶ 960.

FIG. 33 shows a calibration curve 970 obtained by correlating M_(W) ofthe polystyrene standards with the distance between the frequencyresponse curve for toluene 952 and each of the polystyrene solutions954, 956, 958, 960 of FIG. 32. This distance was calculated using theexpression: $\begin{matrix}{{d_{i} = \sqrt{\frac{1}{f_{1} - f_{0}}{\int_{f_{0}}^{f_{1}}{\left( {R_{0} - R_{i}} \right)^{2}{f}}}}},} & {XII}\end{matrix}$

where f₀ and f₁ are the lower and upper frequencies of the responsecurve, respectively; R₀ is the frequency response of the resonator intoluene, and R₁ is the resonator response in a particularpolystyrene-toluene solution. Given response curves for an unknownpolystyrene-toluene mixture and pure toluene 952 (FIG. 32), the distancebetween the two curves can be determined from equation XII. Theresulting d_(i) can be located along the calibration curve 970 of FIG.33 to determine M_(W) for the unknown polystyrene-toluene solution.

Illustrative Example of Measurement of Gas-Phase Reactant Consumption byPressure Monitoring and Control

FIG. 34 depicts the pressure recorded during solution polymerization ofethylene to polyethylene. The reaction was carried out in an apparatussimilar to that shown in FIG. 31. An ethylene gas source was used tocompensate for ethylene consumed in the reaction. A valve, under controlof a processor, admitted ethylene gas into the reaction vessel when thevessel head space pressure dropped below P_(L)≈16.1 psig due toconsumption of ethylene. During the gas filling portion of the cycle,the valve remained open until the head space pressure exceededP_(H)≈20.3 psig.

FIG. 35 and FIG. 36 show ethylene consumption rate as a function oftime, and the mass of polyethylene formed as a function of ethyleneconsumed, respectively. The average ethylene consumption rate, −r_(C2,k)(atm min⁻¹), was determined from the expression $\begin{matrix}{{- r_{{C2},k}} = \frac{\left( {P_{H} - P_{L}} \right)_{k}}{\Delta \quad t_{k}}} & {XIII}\end{matrix}$

where subscript k refers to a particular valve cycle, and Δt_(k) is thetime interval between the valve closing during the present cycle and thevalve opening at the beginning of the next cycle. As shown in FIG. 35,the constant ethylene consumption rate at later times results fromcatalyzed polymerization of ethylene. The high ethylene consumption rateearly in the process results primarily from transport of ethylene intothe catalyst solution prior to establishing an equilibrium ethyleneconcentration in the liquid phase. FIG. 36 shows the amount ofpolyethylene produced as a function of the amount of ethylene consumedby reaction. The amount of polyethylene produced was determined byweighing the reaction products, and the amount of ethylene consumed byreaction was estimated by multiplying the constant average consumptionrate by the total reaction time. A linear least-squares fit to thesedata yields a slope which matches the value predicted from the ideal gaslaw and from knowledge of the reaction temperature and the total volumeoccupied by the gas (the product of vessel head space and number ofvalve cycles during the reaction).

Automated, High Pressure Injection System

FIG. 37 shows a perspective view of an eight-vessel reactor module 1000,of the type shown in FIG. 10, which is fitted with an optional liquidinjection system 1002. The liquid injection system 1002 allows additionof liquids to pressurized vessels, which, as described below, alleviatesproblems associated with pre-loading vessels with catalysts. Inaddition, the liquid injection system 1002 improves concurrent analysisof catalysts by permitting screening reactions to be selectivelyquenched through the addition of a liquid-phase catalyst poison.

The liquid injection system 1002 helps solve problems concerningliquid-phase catalytic polymerization of a gaseous monomer. When usingthe reactor module 390 shown in FIG. 10 to screen or characterizepolymerization catalysts, each vessel is normally loaded with a catalystand solvent prior to reaction. After sealing, gaseous monomer isintroduced into each vessel at a specified pressure to initiatepolymerization. As discussed in Example 1, during the early stages ofreaction, the monomer concentration in the solvent increases as gaseousmonomer dissolves in the solvent. Although the monomer eventuallyreaches an equilibrium concentration in the solvent, catalyst activitymay be affected by the changing monomer concentration prior toequilibrium. Moreover, as the monomer dissolves in the solvent early inthe reaction, additional gaseous monomer is added to maintain thepressure in the vessel headspace. This makes it difficult to distinguishbetween pressure changes in the vessels due to polymerization in theliquid phase and pressure changes due to monomer transport into thesolvent to establish an equilibrium concentration. These analyticaldifficulties can be avoided using the liquid injection system 1002,since the catalyst can be introduced into the vessels after the monomerhas attained an equilibrium concentration in the liquid phase.

The liquid injection system 1002 of FIG. 37 also helps solve problemsthat arise when using the reactor module 390 shown in FIG. 10 toinvestigate catalytic co-polymerization of gaseous and liquidco-monomers. Prior to reaction, each vessel is loaded with a catalystand the liquid co-monomer. After sealing the vessels, gaseous co-monomeris introduced into each vessel to initiate co-polymerization. However,because appreciable time may elapse between loading of liquid componentsand contact with the gaseous co-monomer, the catalyst mayhomo-polymerize a significant fraction of the liquid co-monomer. Inaddition, the relative concentration of the co-monomers in theliquid-phase changes during the early stages of reaction as the gaseousco-monomer dissolves in the liquid phase. Both effects lead toanalytical difficulties that can be avoided using the liquid injectionsystem 1002, since catalysts can be introduced into the vessels afterestablishing an equilibrium concentration of the gaseous and liquidco-monomers in the vessels. In this way, the catalyst contacts the twoco-monomers simultaneously.

The liquid injector system 1002 shown in FIG. 37 also allows users toquench reactions at different times by adding a liquid phase catalystpoison, which improves screening of materials exhibiting a broad rangeof catalytic activity. When using the reactor module 390 of FIG. 10 toconcurrently evaluate library members for catalytic performance, theuser may have little information about the relative activity of librarymembers. If every reaction is allowed to proceed for the same amount oftime, the most active catalysts may generate an excessive amount ofproduct, which can hinder post reaction analysis and reactor clean up.Conversely, the least active catalysts may generate an amount of productinsufficient for characterization. By monitoring the amount of productin each of the vessels—through the use of mechanical oscillators orphase lag measurements, for instance—the user can stop a particularreaction by injecting the catalyst poison into the vessels once apredetermined conversion is achieved. Thus, within the same reactor andin the same experiment, low and high activity catalysts may undergoreaction for relatively long and short time periods, respectively, withboth sets of catalysts generating about the same amount of product.

Referring again to FIG. 37, the liquid injection system 1002 comprisesfill ports 1004 attached to an injector manifold 1006. An injectoradapter plate 1008, sandwiched between an upper plate 1010 and block1012 of the reactor module 1000, provides conduits for liquid flowbetween the injector manifold 1006 and each of the wells or vessels (notshown) within the block 1012. Chemically inert valves 1014 attached tothe injector manifold 1006 and located along flow paths connecting thefill ports 104 and the conduits within the adapter plate 1008, are usedto establish or prevent fluid communication between the fill ports 1004and the vessels or wells. Normally, the liquid injection system 1002 isaccessed through the fill ports 1004 using a probe 1016, which is partof an automated liquid delivery system such as the robotic materialhandling system 146 shown in FIG. 2. However, liquids can be manuallyinjected into the vessels through the fill ports 1004 using a pipette,syringe, or similar liquid delivery device. Conventional high-pressureliquid chromatography loop injectors can be used as fill ports 1004.Other useful fill ports 1004 are shown in FIG. 38 and FIG. 39.

FIG. 38 shows a cross sectional view of a first embodiment of a fillport 1004′ having an o-ring seal to minimize liquid leaks. The fill port1004′ comprises a generally cylindrical fill port body 1040 having afirst end 1042 and a second end 1044. An axial bore 1046 runs the lengthof the fill port body 1040. An elastomeric o-ring 1048 is seated withinthe axial bore 1046 at a point where there is an abrupt narrowing 1050,and is held in place with a sleeve 1052 that is threaded into the firstend 1042 of the fill port body 1040. The sleeve 1052 has a center hole1054 that is sized to accommodate the widest part of the probe 1016. Thesleeve 1052 is typically made from a chemically resistant plastic, suchas polyethylethylketone (PEEK), polytetrafluoroelhylene (PTFE), and thelike, which minimizes damage to the probe 1016 and fill port 1004′during liquid injection. To aid in installation and removal, the fillport 1004′ has a knurled first outer surface 1056 located adjacent tothe first end 1042 of the fill port 1004′, and a threaded second outersurface 1058, located adjacent to the second end 1044 of the fill port1004′.

FIG. 38 also shows the position of the probe 1016 during liquidinjection. Like a conventional pipette, the probe 1016 is a cylindricaltube having an outer diameter (OD) at the point of liquid delivery thatis smaller than the OD over the majority of the probe 1016 length. As aresult, near the probe tip 1060, there is a transition zone 1062 wherethe probe 1016 OD narrows. Because the inner diameter (ID) of the o-ring1048 is about the same as the OD of the probe tip 1060, a liquid-tightseal is formed along the probe transition zone 1060 during liquidinjection.

FIG. 39 shows a second embodiment of a fill port 1004″. Like the firstembodiment 1004′ shown in FIG. 38, the second embodiment 1004″ comprisesa generally cylindrical fill port body 1040′ having a first end 1042′and a second end 1044′. But instead of an o-ring, the fill port 1004″shown in FIG. 39 employs an insert 1080 having a tapered axial hole 1082that results an interference fit, and hence a seal, between the probetip 1060 and the ID of the tapered axial hole 1082 during liquidinjection. The insert 1080 can be threaded into the first end 1042′ ofthe fill port 1004″. Typically, the insert 1080 is made from achemically resistant plastic, such as PEEK, PTFE, and the like, whichminimizes damage to the probe 1016 and fill port 1004″ during liquidinjection. To aid in removal and installation, the fill port′ has aknurled first outer surface 1056′ located adjacent to the first end1042′ of the fill port 1004″, and a threaded second outer surface 1058′located adjacent to the second end 1044′ of the fill port 1004″.

FIG. 40 shows a phantom front view of the injector manifold 1006. Theinjector manifold 1006 includes a series of fill port seats 1100 locatedalong a top surface 1102 of the injector manifold 1006. The fill portseats 1100 are dimensioned to receive the second ends 1044, 1044′ of thefill ports 1004′, 1004″ shown in FIG. 38 and FIG. 39. Locating holes1104, which extend through the injector manifold 1006, locate the valves1014 of FIG. 37 along the front of the injector manifold 1006.

An alternative design for the valve 1014, which is used with theinjection ports is shown is FIG. 40A and FIG. 40B. FIG. 40A shows theinjector manifold 1006, which is shown in a cross sectional view in FIG.40B. The alternative valve design is essentially a check valve that hasa spring 2005 under a poppet 2006. When not injecting, the spring 2005assisted by the pressure of the reaction vessel pushes the poppet 2006against a seal 2007 to seal the reaction vessel. The seal may be of atype known to those of skill in the art, such as an o-ring seal. Wheninjecting, a pump associated with the probe 1016 forces the material tobe injected against the poppet 2006 overcoming the pressure in thechamber and the spring 2005 force to allow the material being injectedto flow past the poppet into the reaction vessel via the channel in themodule.

FIG. 41 shows a cross sectional view of the injector manifold 1006 alonga first section line 1106 of FIG. 40. The cross section illustrates oneof a group of first flow paths 1130. The first flow paths 1130 extendfrom the fill port seats 1100, through the injector manifold 1006, tovalve inlet seats 1132. Each of the valve inlet seats 1132 isdimensioned to receive an inlet port (not shown) of one of the valves1014 depicted in FIG. 37. The first flow paths 1130 thus provide fluidcommunication between the fill ports 1004 and the valves 1014 of FIG.37.

FIG. 42 shows a cross sectional view of the injector manifold 1006 alonga second section line 1108 of FIG. 40. The cross section illustrates oneof a group of second flow paths 1150. The second flow paths 1 150 extendfrom valve outlet seats 1152, through the injector manifold 1006, tomanifold outlets 1154 located along a back surface 1156 of the injectormanifold 1006. Each of the valve outlet seats 1152 is dimensioned toreceive an outlet port (not shown) of one of the valves 1014 depicted inFIG. 37. The manifold outlets 1154 mate with fluid conduits on theinjector adapter plate 1008. Annular grooves 1158, which surround themanifold outlets 1154, are sized to receive o-rings (not shown) thatseal the fluid connection between the manifold outlets 1154 and thefluid conduits on the injector adapter plate 1008. The second flow paths1150 thus provide fluid communication between the valves 1014 and theinjector adapter plate 1008.

FIG. 43 shows a phantom top view of the injector adapter plate 1008,which serves as an interface between the injector manifold 1006 and theblock 1012 of the reactor module 1000 shown in FIG. 37. The injectoradapter plate 1008 comprises holes 1180 that provide access to thevessels and wells within the block 1012. The injector adapter plate 1008also comprises conduits 1182 extending from a front edge 1184 to thebottom surface of the adapter plate 1008. When the adapter plate 1008 isassembled in the reactor module 1000, inlets 1186 of the conduits 1182make fluid connection with the manifold outlets 1154 shown in FIG. 42.

As shown in FIG. 44, which is a cross sectional side view of theinjector adapter plate 1008 along a section line 1188 of FIG. 43, theconduits 1182 terminate on a bottom surface 1210 of the injector plate1008 at conduit outlets 1212. The bottom surface 1210 of the adapterplate 1008 forms an upper surface of each of the wells in the reactormodule 1000 block 1012 of FIG. 37. To ensure that liquid is properlydelivered into the reaction vessels, elongated well injectors, as shownin FIG. 45 and FIG. 48 below, are connected to the conduit outlets 1212.

FIG. 45 shows an embodiment of a well injector 1230. The well injector1230 is a generally cylindrical tube having a first end 1232 and asecond end 1234. The well injector 1230 has a threaded outer surface1236 near the first end 1232 so that it can be attached to threadedconduit outlets 1212 shown in FIG. 44. Flats 1238 located adjacent tothe threaded outer surface 1236 assist in twisting the first end 1232 ofthe well injector 1230 into the conduit outlets 1212. The length of thewell injector 1230 can be varied. For example, the second end 1234 ofthe well injector 1230 may extend into the liquid mixture;alternatively, the second end 1234 of the injector 1230 may extend aportion of the way into the vessel headspace. Typically, the wellinjector 1230 is made from a chemically resistant plastic, such PEEK,PTFE, and the like.

Liquid injection can be understood by referring to FIGS. 46-48. FIG. 46shows a top view of the reactor module 1000, and FIG. 47 and FIG. 48show, respectively, cross sectional side views of the reactor module1000 along first and second section lines 1260, 1262 shown in FIG. 46.Prior to injection of a catalyst or other liquid reagent, the probe1016, which initially contains a first solvent, withdraws apredetermined amount of the liquid reagent from a reagent source. Next,the probe 1016 withdraws a predetermined amount of a second solvent froma second solvent source, resulting in a slug of liquid reagent suspendedbetween the first and second solvents within the probe 1016. Generally,probe manipulations are carried out using a robotic material handlingsystem of the type shown in FIG. 2, and the second solvent is the sameas the first solvent.

FIGS. 47 and 48 show the inlet and outlet paths of the valve 1014 priorto, and during, liquid injection, respectively. Once the probe 1016contains the requisite amount of liquid reagent and solvents, the probetip 1058 is inserted in the fill port 1004, creating a seal as shown,for example, in FIG. 38 and FIG. 39. The valve 1014 is then opened, andthe second solvent, liquid reagent, and a portion of the first solventare injected into the reactor module 1000 under pressure. From the fillport 1004, the liquid flows into the injector manifold 1006 through oneof the first flow paths 1130 that extend from the fill port seats 1100to the valve inlet seats 1132. The liquid enters the valve 1014 throughan inlet port 1280, flows through a valve flow path 1282, and exits thevalve 1014 through an outlet port 1284. After leaving the valve 1014,the liquid flows through one of the second flow paths 1150 to a manifoldoutlet 1154. From the manifold outlet 1154, the liquid flows through theinjector adapter plate 1008 within one of the fluid conduits 1182, andis injected into a reactor vessel 1286 or well 1288 through the wellinjector 1230. In the embodiment shown in FIG. 48, the second end 1234of the well injector 1230 extends only a fraction of the way into thevessel headspace 1290. In other cases, the second end 1234 may extendinto the reaction mixture 1292.

Liquid injection continues until the slug of liquid reagent is injectedinto the reactor vessel 1286 and the flow path from the fill port 1004to the second end 1234 of the well injector 1230 is filled with thefirst solvent. At that point, the valve 1014 is closed, and the probe1016 is withdrawn from the fill port 1004.

Reactor Vessel Pressure Seal and Magnetic Feed-Through StirringMechanism

FIG. 48 shows a stirring mechanism and associated seals for maintainingabove-ambient pressure in the reactor vessels 1286. The direct-drivestirring mechanism 1310 is similar to the one shown in FIG. 10, andcomprises a gear 1312 attached to a spindle 1314 that rotates a blade orpaddle 1316. A dynamic lip seal 1318, which is secured to the upperplate 1010 prevents gas leaks between the rotating spindle 1314 and theupper plate 1010. When newly installed, the lip seal is capable ofmaintaining pressures of about 100 psig. However, with use, the lip seal1318, like o-rings and other dynamic seals, will leak due to frictionalwear. High service temperatures, pressures, and stirring speeds hastendynamic seal wear.

FIG. 49 shows a cross sectional view of a magnetic feed through 1340stirring mechanism that helps minimize gas leaks associated with dynamicseals. The magnetic feed-through 1340 comprises a gear 1342 that isattached to a magnetic driver assembly 1344 using cap screws 1346 orsimilar fasteners. The magnetic driver assembly 1344 has a cylindricalinner wall 1348 and is rotatably mounted on a rigid cylindrical pressurebarrier 1350 using one or more bearings 1352. The bearings 1352 arelocated within an annular gap 1354 between a narrow head portion 1356 ofthe pressure barrier 1350 and the inner wall 1348 of the magnetic driverassembly 1344. A base portion 1358 of the pressure barrier 1350 isaffixed to the upper plate 1010 of the reactor module 1000 shown in FIG.48 so that the axis of the pressure barrier 1350 is about coincidentwith the centerline of the reactor vessel 1286 or well 1288. Thepressure barrier 1350 has a cylindrical interior surface 1360 that isopen only along the base portion 1358 of the pressure barrier 1350.Thus, the interior surface 1360 of the pressure barrier 1350 and thereactor vessel 1286 or well 1288 define a closed chamber.

As can be seen in FIG. 49, the magnetic feed through 1340 furthercomprises a cylindrical magnetic follower 1362 rotatably mounted withinthe pressure barrier 1350 using first 1364 and second 1366 flangedbearings. The first 1364 and second 1366 flanged bearings are located infirst 1368 and second 1370 annular regions 1368 delimited by theinterior surface 1360 of the pressure barrier 1350 and relatively narrowhead 1372 and leg 1374 portions of the magnetic follower 1362,respectively. A keeper 1376 and retaining clip 1378 located within thesecond annular region 1370 adjacent to the second flanged bearing 1366help minimize axial motion of the magnetic follower 1362. A spindle (notshown) attached to the free end 1380 of the leg 1374 of the magneticfollower 1362, transmits torque to the paddle 1316 immersed in thereaction mixture 1292 shown in FIG. 48.

During operation, the rotating gear 1342 and magnetic driver assembly1344 transmit torque through the rigid pressure barrier 1350 to thecylindrical magnetic follower 1362. Permanent magnets (not shown)embedded in the magnetic driver assembly 1344 have force vectors lyingin planes about perpendicular to the axis of rotation 1382 of themagnetic driver assembly 1344 and follower 1362. These magnets arecoupled to permanent magnets (not shown) that are similarly aligned andembedded in the magnetic follower 1362. Because of the magneticcoupling, rotation of the driver assembly 1344 induces rotation of thefollower 1362 and stirring blade or paddle 1316 of FIG. 48. The follower1362 and paddle 1316 rotate at the same frequency as the magnetic driverassembly, though, perhaps, with a measurable phase lag.

Removable and Disposable Stirrer

The stirring mechanism 1310 shown in FIG. 48 includes a multi-piecespindle 1314 comprising an upper spindle portion 1400, a coupler 1402,and a removable stirrer 1404. The multi-piece spindle 1314 offerscertain advantages over a one-piece spindle. Typically, only the upperdrive shaft 1400 and the coupler 1402 are made of a high modulusmaterial such as stainless steel: the removable stirrer 1404 is made ofa chemically resistant and inexpensive plastic, such as PEEK, PTFE, andthe like. In contrast, one-piece spindles, though perhaps coated withPTFE, are generally made entirely of a relatively expensive high modulusmaterial, and are therefore normally reused. However, one-piece spindlesare often difficult to clean after use, especially following apolymerization reaction. Furthermore, reaction product may be lostduring cleaning, which leads to errors in calculating reaction yield.With the multi-piece spindle 1314, one discards the removable stirrer1404 after a single use, eliminating the cleaning step. Because theremovable stirrer 1404 is less bulky than the one-piece spindle, it canbe included in certain post-reaction characterizations, includingproduct weighing to determine reaction yield.

FIG. 50 shows a perspective view of the stirring mechanism 1310 of FIG.48, and provides details of the multi-piece spindle 1314. A gear 1312 isattached to the upper spindle portion 1400 of the multi-piece spindle1314. The upper spindle 1400 passes through a pressure seal assembly1420 containing a dynamic lip seal, and is attached to the removablestirrer 1404 using the coupler 1402. Note that the removable stirrer1404 can also be used with the magnetic feed through stirring mechanism1340 illustrated in FIG: 49. In such cases, the upper spindle 1400 iseliminated and the leg 1374 of the cylindrical magnetic follower 1362 orthe coupler 1402 or both are modified to attach the magnetic follower1362 to the removable stirrer 1404.

FIG. 51 shows details of the coupler 1402, which comprises a cylindricalbody having first 1440 and second 1442 holes centered along an axis ofrotation 1444 of the coupler 1402. The first hole 1440 is dimensioned toreceive a cylindrical end 1446 of the upper spindle 1400. A shoulder1448 formed along the periphery of the upper spindle 1400 rests againstan annular seat 1450 located within the first hole 1440. A set screw(not shown) threaded into a locating hole 1452 prevents relative axialand rotational motion of the upper spindle 1400 and the coupler 1402.

Referring to FIGS. 50 and 51, the second hole 1442 of the coupler 1402is dimensioned to receive a first end 1454 of the removable stirrer1404. A pin 1456, which is embedded in the first end 1454 of theremovable stirrer, cooperates with a locking mechanism 1458 located onthe coupler 1402, to prevent relative rotation of the coupler 1402 andthe removable stirrer 1404. The locking mechanism 1458 comprises anaxial groove 1460 formed in an inner surface 1462 of the coupler. Thegroove 1460 extends from an entrance 1464 of the second hole 1442 to alateral portion 1466 of a slot 1468 cut through a wall 1470 of thecoupler 1402.

As shown in FIG. 52, which is a cross sectional view of the coupler 1402along a section line 1472, the lateral portion 1466 of the slot 1468extends about 60 degrees around the circumference of the coupler 1402 toan axial portion 1474 of the slot 1468. To connect the removable stirrer1404 to the coupler 1402, the first end 1454 of the removable stirrer1404 is inserted into the second hole 1442 and then rotated so that thepin 1456 travels in the axial groove 1460 and lateral portion 1466 ofthe slot 1468. A spring 1476, mounted between the coupler 1402 and ashoulder 1478 formed on the periphery of the removable stirrer 1404,forces the pin 1456 into the axial portion 1474 of the slot 1468.

An alternative design for the multi-piece spindle 1314 is shown in FIG.50A, which has an upper spindle portion 1400, a coupler 1402 and aremovable stirrer 1404. The details of this alternative design are shownin FIG. 50B. This alternative design is essentially a spring lockmechanism that allows for quick removal of the removable stirrer 1404.The removable stirrer 1404 is locked in to the coupling mechanism by aseries of balls 2001 that are held into a groove in the removablestirrer 1404 by a collar 2002, which is part of the coupler 1402. Theremovable stirrer 1404 is released by pulling the collar 2002 backagainst a spring 2003 and allowing the balls 2001 to fall into a pocketin the collar 2002 and releasing the removable stirrer.

Parallel Pressure Reactor Control and Analysis

FIG. 53 shows one implementation of a computer-based system formonitoring the progress and properties of multiple reactions in situ.Reactor control system 1500 sends control data 1502 to and receivesexperimental data 1504 from reactor 1506. As will be described in moredetail below, in one embodiment reactor 1506 is a parallelpolymerization reactor and the control and experimental data 1502 and1504 include set point values for temperature, pressure, time andstirring speed as well as measured experimental values for temperatureand pressure. Alternatively, in other embodiments reactor 1506 can beany other type of parallel reactor or conventional reactor, and data1502, 1504 can include other control or experimental data. Systemcontrol module 1508 provides reactor 1506 with control data 1502 basedon system parameters obtained from the user through user I/O devices1510, such as a display monitor, keyboard or mouse. Alternatively,system control module 1508 can retrieve control data 1502 from storage1512.

Reactor control system 1500 acquires experimental data 1504 from reactor1506 and processes the experimental data in system control module 1508and data analysis module 1514 under user control through user interfacemodule 1516. Reactor control system 1500 displays the processed databoth numerically and graphically through user interface module 1516 anduser I/O devices 1510, and optionally through printer 1518.

FIG. 54 illustrates an embodiment of reactor 1506 in which pressure,temperature, and mixing intensity are automatically controlled andmonitored. Reactor 1506 includes reactor block 1540, which containssealed reactor vessels 1542 for receiving reagents. In one embodiment,reactor block 1540 is a single unit containing each of reactor vessels1542. Alternatively, reactor block 1540 can include a number of reactorblock modules, each of which contains a number of reactor vessels 1542.Reactor 1506 includes a mixing control and monitoring system 1544, atemperature control and monitoring system 1546 and a pressure controland monitoring system 1548. These systems communicate with reactorcontrol system 1500.

The details of mixing control and monitoring system 1544 are illustratedin FIG. 55. Each of reactor vessels 1542 contains a stirrer 1570 formixing the vessel contents. In one embodiment, stirrers 1570 arestirring blades mounted on spindles 1572 and driven by motors 1574.Separate motors 1574 can control each individual stirrer 1570;alternatively, motors 1574 can control groups of stirrers 1570associated with reactor vessels 1542 in separate reactor blocks. Inanother embodiment, magnetic stirring bars or other known stirringmechanisms can be used. System control module 1508 provides mixingcontrol signals to stirrers 1570 through interface 1576, 1578, and oneor more motor cards 1580. Interface 1576, 1578 can include a commercialmotor driver 1576 and motor interface software 1578 that providesadditional high level motor control, such as the ability to initializemotor cards 1580, to control specific motors or motor axes (where eachmotor 1580 controls a separate reactor block), to set motor speed andacceleration, and to change or stop a specified motor or motor axis.

Mixing control and monitoring system 1544 can also include torquemonitors 1582, which monitor the applied torque in each of reactorvessels 1542. Suitable torque monitors 1582 can include optical sensorsand magnetic field sensors mounted on spindles 1572, or strain gauges(not shown), which directly measure the applied torque and transmittorque data to system control module 1508 and data analysis module 1514.Monitors 1582 can also include encoders, resolvers, Hall effect sensorsand the like, which may be integrated into motors 1574. These monitorsmeasure the power required to maintain a constant spindle 1572rotational speed, which is related to applied torque.

Referring to FIG. 56, temperature control and monitoring system 1546includes a temperature sensor 1600 and a heating element 1602 associatedwith each reactor vessel 1542 and controlled by temperature controller1604. Suitable heating elements 1602 can include thin filamentresistance heaters, thermoelectric devices, thermistors, or otherdevices for regulating vessel temperature. Heating elements can includedevices for cooling, as well as heating, reactor vessels 1542. Systemcontrol unit 1508 transmits temperature control signals to heatingelements 1602 through interface 1606, 1608 and temperature controller1604. Interface 1606, 1608 can include a commercial temperature devicedriver 1606 implemented to use hardware such as an RS232 interface, andtemperature interface software 1608 that provides additional high levelcommunication with temperature controller 1604, such as the ability tocontrol the appropriate communication port, to send temperature setpoints to temperature controller 1604, and to receive temperature datafrom temperature controller 1604.

Suitable temperature sensors 1600 can include thermocouples, resistancethermoelectric devices, thermistors, or other temperature sensingdevices. Temperature controller 1604 receives signals from temperaturesensors 1600 and transmits temperature data to reactor control system1500. Upon determining that an increase or decrease in reactor vesseltemperature is appropriate, system control module 1508 transmitstemperature control signals to heating elements 1602 through heatercontroller 1604. This determination can be based on temperatureparameters entered by the user through user interface module 1516, or onparameters retrieved by system control module 1508 from storage. Systemcontrol module 1508 can also use information received from temperaturesensors 1600 to determine whether an increase or decrease in reactorvessel temperature is necessary.

As shown in FIG. 57, pressure control and monitoring system 1548includes a pressure sensor 1630 associated with each reactor vessel1542. Each reactor vessel 1542 is furnished with a gas inlet/outlet 1632that is controlled by valves 1634. System control module 1508 controlsreactor vessel pressure through pressure interface 1636, 1638 andpressure controller 1640. Pressure interface 1636, 1638 can beimplemented in hardware, software or a combination of both. Pressurecontroller 1640 transmits pressure control signals to valves 1634allowing gases to enter or exit reactor vessels 1542 throughinlet/outlet 1632 as required to maintain reactor vessel pressure at alevel set by the user through user interface 1516.

Pressure sensors 1630 obtain pressure readings from reactor vessels 1542and transmit pressure data to system control module 1508 and dataanalysis module 1514 through pressure controller 1640 and interface1636, 1638. Data analysis module 1514 uses the pressure data incalculations such as the determination of the rate of production ofgaseous reaction products or the rate of consumption of gaseousreactants, discussed in more detail below. System control module 1508uses the pressure data to determine when adjustments to reactor vesselpressure are required, as discussed above.

FIG. 58 is a flow diagram illustrating the operation of a reactorcontrol system 1500. The user initializes reactor control system 1500 bysetting the initial reaction parameters, such as set points fortemperature, pressure and stirring speed and the duration of theexperiment, as well as selecting the appropriate hardware configurationfor the experiment (step 1660). The user can also set other reactionparameters that can include, for example, a time at which additionalreagents, such as a liquid co-monomer in a co-polymerization experiment,should be added to reaction vessels 1542, or a target conversionpercentage at which a quenching agent should be added to terminate acatalytic polymerization experiment. Alternatively, reactor controlsystem 1500 can load initial parameters from storage 1512. The userstarts the experiment (step 1662). Reactor control system 1500 sendscontrol signals to reactor 10, causing motor, temperature and pressurecontrol systems 1544, 1546 and 1548 to bring reactor vessels 1542 to setpoint levels (step 1664).

Reactor control system 1500 samples data through mixing monitoringsystem 1544, temperature monitoring system 1546 and pressure monitoringsystem 1548 at sampling rates, which may be entered by the user (step1666). Reactor control system 1500 can provide process control bytesting the experimental data, including sampled temperature, pressureor torque values as well as elapsed time, against initial parameters(step 1668). Based on these inputs, reactor control system 1500 sendsnew control signals to the mixing, temperature and/or pressure controland monitoring systems of reactor 1506 (steps 1670, 1664). These controlsignals can also include instructions to a material handling robot toadd material, such as a reagent or a catalyst quenching agent, to one ormore reactor vessels based upon experimental data such as elapsed timeor percent conversion calculated as discussed below.

The user can also enter new parameters during the course of theexperiment, such as changes in motor speed, set points for temperatureor pressure, or termination controlling parameters such as experimenttime or percent conversion target (step 1672), which may also causereactor control system 1500 to send new control signals to reactor 1506(steps 1672, 1670, 1664).

Data analysis module 1514 performs appropriate calculations on thesampled data (step 1674), as will be discussed below, and the resultsare displayed on monitor 1510 (step 1676). Calculated results and/orsampled data can be stored in data storage 1512 for later display andanalysis. Reactor control system 1500 determines whether the experimentis complete—for example, by determining whether the time for theexperiment has elapsed (step 1678). Reactor control system 1500 can alsodetermine whether the reaction occurring in one or more of reactorvessels 1542 has reached a specified conversion target based on resultscalculated in step 1674; in that case, reactor control system 1500causes the addition of a quenching agent to the relevant reactor vesselor vessels as discussed above, terminating the reaction in that vessel.For any remaining reactor vessels, reactor control system 1500 samplesadditional data (step 1666) and the cycle begins anew. When all reactorvessels 1542 in reactor block 1540 have reached a specified terminationcondition, the experiment is complete (step 1680). The user can alsocause the reaction to terminate by aborting the experiment at any time.It should be recognized that the steps illustrated in FIG. 58 are notnecessarily performed in the order shown; instead, the operation ofreactor control system 1500 can be event driven, responding, forexample, to user events, such as changes in reaction parameters, orsystem generated periodic events.

Analysis of Experimental Data

The type of calculation performed by data analysis module 1514 (step1674) depends on the nature of the experiment. As discussed above, whilean experiment is in progress, reactor control system 1500 periodicallyreceives temperature, pressure and/or torque data from reactor 1506 atsampling rates set by the user (step 1666). System control module 1508and data analysis module 1514 process the data for use in screeningmaterials or for performing quantitative calculations and for display byuser interface module 1516 in formats such as those shown in FIGS. 63-64and 65.

Reactor control system 1500 uses temperature measurements fromtemperature sensors 1600 as a screening criteria or to calculate usefulprocess and product variables. For instance, in one implementation,catalysts of exothermic reactions are ranked based on peak reactiontemperature reached within each reactor vessel, rates of change oftemperature with respect to time, or total heat released over the courseof reaction. Typically, the best catalysts of an exothermic reaction arethose that, when combined with a set of reactants, result in thegreatest heat production in the shortest amount of time. In otherimplementations, reactor control system 1500 uses temperaturemeasurements to compute rates of reaction and conversion.

In addition to processing temperature data as a screening tool, inanother implementation, reactor control system 1500 uses temperaturemeasurement—combined with proper thermal management and design of thereactor system—to obtain quantitative calorimetric data. From such data,reactor control system 1500 can, for example, compute instantaneousconversion and reaction rate, locate phase transitions (e.g., meltingpoint, glass transition temperature) of reaction products, or measurelatent heats to deduce structural information of polymeric materials,including degree of crystallinity and branching. For details ofcalorimetric data measurement and use, see description accompanying FIG.9 and equations I-V.

Reactor control system 1500 can also monitor mixing variables such asapplied stirring blade torque in order to determine the viscosity of thereaction mixture and related properties. Reactor control system 1500 canuse such data to monitor reactant conversion and to rank or characterizematerials based on molecular weight or particle size. See, for example,the description of equations VI-VIII above.

Reactor control system 1500 can also assess reaction kinetics bymonitoring pressure changes due to production or consumption of variousgases during reaction. Reactor control system 1500 uses pressure sensors1630 to measure changes in pressure in each reactor vessel headspace—thevolume within each vessel that separates the liquid reagents from thevessel's sealed cap. During reaction, any changes in the head spacepressure, at constant temperature, reflect changes in the amount of gaspresent in the head space. As described above (equation XI), reactorsystem 1500 uses this pressure data to determine the molar production orconsumption rate, r_(i), of a gaseous component.

Operation of a Reactor Control System

Referring to FIG. 59, reactor control system 1500 receives systemconfiguration information from the user through system configurationwindow 1700, displayed on monitor 150. System configuration window 1700allows the user to specify the appropriate hardware components for anexperiment. For example, the user can choose the number of motor cards1580 and the set a number of motor axes per card in motor pane 1702.Temperature controller pane 1704 allows the user to select the number ofseparate temperature controllers 1604 and the number of reactor vessels(the number of feedback control loops) per controller. In pressuresensor pane 1706, the user can set the number of pressure channelscorresponding to the number of reactor vessels in reactor 1506. The usercan also view the preset safety limits for motor speed, temperature andpressure through system configuration window 1700.

As shown in FIG. 60, reactor control system 1500 receives data displayinformation from the user through system option window 1730. Displayinterval dialog 1732 lets the user set the refresh interval for datadisplay. The user can set the number of temperature and pressure datapoints kept in memory in data point pane 1734.

At any time before or during an experiment, the user can enter or modifyreaction parameters for each reactor vessel 1542 in reactor block 1540using reactor setup window 1760, shown in FIG. 61. In motor setup pane1762, the user can set a motor speed (subject to any preset safetylimits), and can also select single or dual direction motor operation.The user can specify temperature parameters in temperature setup pane1764. These parameters include temperature set point 1766, turn offtemperature 1768, sampling rate 1770, as well as the units fortemperature measurement and temperature controller operation modes. Byselecting gradient button 1772, the user can also set a temperaturegradient, as will be discussed below. Pressure parameters, including apressure set point and sampling rate, can be set in pressure setup pane1774. Panes 1762, 1764 and 1774 can also display safety limits for motorspeed, temperature and pressure, respectively. The values illustrated inFIG. 61 are not intended to limit this invention and are illustrativeonly. Reactor setup window 1760 also lets the user set a time for theduration of the experiment. Reactor setup window 1760 lets the user saveany settings as defaults for future use, and load previously savedsettings.

FIG. 62 illustrates the setting of a temperature gradient initiated byselecting gradient button 1772. In gradient setup window 1800, the usercan set a temperature gradient across reactor 1506 by entering differenttemperature set points 1802 for each reactor block module of amulti-block reactor 1506. As with other setup parameters, suchtemperature gradients can be saved in reactor setup window 1760.

Referring to FIG. 63, the user can monitor an experiment in reactionwindow 1830. System status pane 1832 displays the current system status,as well as the status of the hardware components selected in systemconfiguration window 1700. Setting pane 1834 and time pane 1836 displaythe current parameter settings and time selected in reactor setup window1760, as well as the elapsed time in the experiment. Experimentalresults are displayed in data display pane 1838, which includes twodimensional array 1840 for numerical display of data pointscorresponding to each reactor vessel 1542 in reactor 1506, and graphicaldisplay 1842 for color display of the data points displayed in array1840. Color display 1842 can take the form of a two dimensional array ofreactor vessels or three dimensional color histogram 1870, shown in FIG.64. The color range for graphical display 1842 and histogram 1870 isdisplayed in legends 1872 and 1874, respectively. Data display pane 1838can display either temperature data or conversion data calculated frompressure measurements as described above. In either case, the displayeddata is refreshed at the rate set in the system options window 1730.

By selecting an individual reactor vessel 1542 in data display pane1838, the user can view a detailed data window 1900 for that vessel, asshown in FIG. 65. Data window 1900 provides a graphical display ofexperimental results, including, for example, temperature, pressure,conversion and molecular weight data for that vessel for the duration ofthe experiment.

Referring again to FIG. 64, toolbar 1876 lets the user set reactorparameters (by entering reactor setup window 1760) and color scaling forcolor displays 1842 and 1870. The user can also begin or end anexperiment, save results and exit system 1500 using toolbar 1876. Theuser can enter any observations or comments in comment box 1878. Usercomments and observations can be saved with experimental results.

Referring to FIG. 66, the user can set the color scaling for colordisplays 1842 and 1870 through color scaling window 1920. Color scalingwindow 1920 lets the user select a color range corresponding totemperature or conversion in color range pane 1922. The user can alsoset a color gradient, either linear or exponential, through colorgradient pane 1924. Color scaling window 1920 displays the selectedscale in color legend 1926.

The invention can be implemented in digital electronic circuitry, or incomputer hardware, firmware, software, or in combinations of them.Apparatus of the invention can be implemented in a computer programproduct tangibly embodied in a machine-readable storage device forexecution by a programmable processor; and method steps of the inventioncan be performed by a programmable processor executing a program ofinstructions to perform functions of the invention by operating on inputdata and generating output. The invention can be implementedadvantageously in one or more computer programs that are executable on aprogrammable system including at least one programmable processorcoupled to receive data and instructions from, and to transmit data andinstructions to, a data storage system, at least one input device, andat least one output device. Each computer program can be implemented ina high-level procedural or object-oriented programming language, or inassembly or machine language if desired; and in any case, the languagecan be a compiled or interpreted language.

Suitable computer programs in modules 1508 and 1514 can be implementedin classes as set forth in the following tables. (The prefix “o” in aname indicates that the corresponding property is a user-defined object;the prefix “c” in a name indicates that the corresponding property is acollection.)

Application class Property Table: Category Name AccessDescription/Comments General ClsName Get Class name AppName GetApplication name sRootDir Get/Let Root directory of all system filesbDebugMode Get/Let System running mode. If TRUE, display message boxesfor errors in addition to error logging. If FALSE, log the error to thelog file DBIsConnected Get/Let Whether database is connected SystemSectionGeneral Get General section Registry SectionSystemLimits GetSection for System Limit Values SectionDefaultParam Get Section forsystem default parameters ColorScaling oTempScale Get Color Scale objectfor temperature data oViscosityScale Get Color Scale object forviscosity data oConversionScale Get Color Scale object for conversiondata oMWScale Get Color Scale object for molecule weight data MethodTable: Argument Name List Return Type Description/Comments SaveCnfgBoolean Save application configurations to the system registry

2. ColorScale class Parent Class: Application Property Table: NameAccess Description/Comments ClsName Get Class name Highest Get/LetHighest value GradientType Get/Let Type of the gradient between thelowest and highest to the log file LegendValues Get A collection oflegend values Method Table: Argument Name List Return TypeDescription/Comments SetLegendValues Recalculate the legend valuesaccording to the current property values GetLegendColor fValue long Getcolor of the specified data value

3. ColorLegend class Parent Class: ColorScale Property Table: NameAccess Description/Comments ClsName Get Class Name ColorCount Get Numberof colors used in the legend Method Table: Argument Name List ReturnType Description/Comments GetColorValue fValue long Get color for thespecified data value

4. System class Property Table: Description/ Category Name AccessComments General ClsName Get ExpID System Status Status Get/Let Statusvariable STATUS_OFF Get constant STATUS_RUN Get constant STATUS_IDLE Getconstant STATUS_ERROR Get constant System Timing oExpTiming Get Controland record the experiment time oDisplayTiming Get Control the datadisplay updating rate System Alarming oAlarm Get Provide alarm whensystem error occurs System Components oMotors Get oHeaters GetoPressures Get Method Table: Argument Name List Return TypeDescription/Comments Run StopRunning Archive

5. ExpTiming class Parent Class: System Property Table: Name AccessDescription/Comments ClsName Get Class Name TimingByTime Get/Let Booleantype TimingByPressure Get/Let Boolean type TimingByTemperature Get/LetBoolean type TargetTime Get/Let System will stop if specified targetvalue is achieved TargetPressure Get/Let System will stop if specifiedtarget value is achieved TargetTemperature Get/Let System will stop ifspecified target value if achieved ExpDate Get/Let Date when experimentstarts to run ExpStartTime Get/Let Time when experiment starts to funExpEndTime Get/Let Time when experiment stop running ExpElapsedTimeGet/Set The time passed during the experiment TimerInterval Let Timerused to update the elapsed time Method Table: Name Argument List ReturnType Description LoadDefaultExpTiming Boolean SaveDefaultExpTimingBoolean

6. DisplayTiming Class Parent Class: System Property Table: Name AccessDescription/Comments ClsName Get Class Name DisplayTimer Get/Set Timerused to update the data TimerIntercal Get/Let Method Table: NameArgument List Return Type Description SaveDefaultParam Boolean

7. Alarm class Parent Class: System Property Table: Name AccessDescription/Comments ClsName Get Class Name BeepTimer Set Timer used tocontrol beep PauseTimer Set Timer used to pause the beep BeepStatus GetA boolean value: FALSE if paused, otherwise TRUE BeepPauseTime Let Timeduration for beep to pause Method Table: Name Argument List Return TypeDescription TurnOnBeep Start to beep TurnOffBeep Stop beeping BeepPauseDisable beep BeepResume Enable beep

8. Motors class Parent Class: System Property Table: Name AccessDescription/Comments ClsName Get Class Name SpeedLimit Get/Let SafetyLimit MotorIsOn Get/Let Status variable Card1AxesCount Get/Let Axescount in card1 Card2AcesCount Get/Let Axes count in card2 oMotorCard1Get Motor card object oMotorCard2 Get Motor card object oSpinTimerGet/Set Timer for dual spin FoundDLL Get Motion DLL ErrCode Get Errorcode Method Table: Argument Return Category Name List Type DescriptionTo/From LoadDefaultParam Boolean system SaveDefaultParam BooleanRegistry SaveCardAxesCount Boolean SaveSystemLimit Boolean Create/CreateCard1 iAxesCount Delete CreateCard2 iAxesCount Card DeleteCard1Objects DeleteCard2 Motor Init Boolean For all axes Control Spin iAxis,Boolean dSpeed run Boolean For all axes StopRunning Boolean For all axesArchive Archiveparam iFileNo Boolean

9. MotorAxis class Parent Class: Motors Property Table: Name AccessDescription/Comments ClsName Get Class Name Parent Set Reference to theparent object MotorID Get/Let Motor Axis ID oCurParam Get Reference tocurrent parameter setting Method Table: Name Argument List Return TypeDescription GetParamSetting [index] MotorParam Return the last in theparameter collection Run Boolean Add oCurParam to the Param collection,and run this motor axis

10. MotorParam class Parent Class: Motors Property Table: Name AccessDescription/Comments clsName Get Class Name Parent Set Reference to theparent object MotionType Get/Let Dual or single direction spin DeltaTGet/Let Time duration before changing spin direction SpinRate Get/LetSpin rate in RPM EffectiveTime Get/Let Time the parameters take effectMethod Table: Name Argument List Return Type Description PrintParamiFileNo Boolean Print the parameters to file

11. Heaters class Parent Class: System Property Table: Name AccessDescription/Comments ClsName Get Class Name oParent Get Reference to theparent object TempLimit Get/Let Temperature Safety Limit SplRateLimitGet/Let Sample Rate Limit CtlrLoopCount Get/Let Loop count incontroller1 CtlrLoopCount Get/Let Loop count in controller2 HeaterIsOnGet/Let Status variable oHeaterCtlr1 Get Heater controller object asclsHeaterCtlr oHeaterCtlr2 Get Heater controller object as clsHeaterCtlroData Get Data object as clsHeaterData 1DataPointsInMem Get/Let Numberof data points kept in memory FoundDLL Get RS232 DLL. If found, 1,otherwise - 1 ErrCode Get Error Code Method Table: Argument ReturnCategory Name List Type Descriptions To/From LoadDefaultParam Booleansystem Registry SaveDefaultParam Boolean SaveCtlrLoopCount BooleanSaveSystemLimit Boolean Create/ Create Ctlr 1 iLoopCount Delete CtlrObjects Create Ctlr 2 iLoopCount Delete Ctlr 1 Delete Ctlr 2 Heater InitBoolean Open Control COM1,COM2 OutputHeat Boolean For all loops TurnOffBoolean For all loops GetTemp Boolean For all loops SafetyMonitorIcount,vData Check Temperature SafetyHandler Archive ArchiveParamiFileNo Boolean

12. HeaterCtlr class Parent Class: Heaters Property Table: Name AccessDescription/Comments ClsName Get Class Name Parent Set Reference to theparent object oCurParam Get Reference to current parameter settingMethod Table: Argument Return Name List Type Description AddParamSettingoParam Boolean Add the parameter object to the parameter collectionGetParamSetting [index] HeaterParam Return the last in the parametercollection

13. HeaterParam class Parent Class: HeaterCtlr Property Table: NameAccess Description/Comments clsName Get Class Name Parent Set Referenceto the parent object Setpoint Get/Let Setpoint for temperature SplRateGet/Let Sampling Rate (Hz) EffectiveTime Get/Let Time the parameterstake effect Method Table: Name Argument List Return Type DescriptionPrintParam iFileNo Boolean Print the parameters to file

14. HeaterData class Parent Class: Heaters Property Table: Name AccessDescription/Comments clsName Get Class Name Parent Set Reference to theparent object DataPointsInMem Let LoopCount Let Total loop countDataCount Get Data point count cTime Get Get time data collection cTempGet Get temperature data collection Method Table: Argument Return NameList Type Description GetData ByRef fTime, Boolean Get current data set,or the data ByRef vTemp set with specified index [,index] AddData fTime,vTemp Add the data set to the data collections ClearData Clear the datacollection WriteToDisk Write the current data to disk file

15. Pressures class Parent Class: System Property Table: Name AccessDescription/Comments ClsName Get Class Name oParent Get Reference to theparent object PressureLimit Get/Let Pressure Safety Limit SplRateLimitGet/Let Sample Rate Limit ChannelCount Get/Let Analog Input channelcount PressureIsOn Get/Let Status variable oData Get Data object asclsPressureData 1DataPointsInMem Get/Let Number of data points kept inmemory oCWAOP Get Object of analog output ActiveX control oCWAIP GetObject of analog input ActiveX control ErrCode Get Error code MethodTable: Argu- ment Return Category Name List Type Description To/FromLoadDefaultParam Boolean System Registry SaveDefaultParam BooleanSaveChannelCount Boolean SaveDataPointsInMem SaveSystemLimit BooleanPressure AnalogOutput Boolean Output Pset System GetAIData BooleanAnalog Input Control Archive ArchiveParam iFileNo Boolean

16. PressureParam class Parent Class: Pressures Property Table: NameAccess Description/Comments clsName Get Class Name Parent Set Referenceto the parent object Setpoint Get/Let Setpoint for pressure (psi)SplRate Get/Let Sampling Rate (Hz) EffectiveTime Get/Let Time theparameters take effect Method Table: Return Name Argument List TypeDescription PrintParam iFileNo Boolean Print the parameters to the file

17. PressureData class Parent Class: Pressures Property Table: NameArgument Access Description/Comments clsName Get Class Name Parent SetReference to the parent object DataPointsInMem Let ChannelCount LetTotal AI channel count PresCount Get Pressure data point count ConvCountGet Conversion data point count cPresTime Get Get time collection forpressure data cPressure Get Get pressure data collection cConvTimeiChannelNo Get Get time collection for conversion data cConversioniChannelNo Get Get conversion data collection Method Table: Return NameArgument List Type Description GetCurPres ByRef vPres Boolean Getcurrent pressure data set GetCurConv ByRef vConv Boolean Get currentconversion data set AddPres fTime, vPres Add the pressure data set tothe pressure data col- lections, then calculate conversions ClearDataClear all the data collections WritePresToDisk Boolean Write the currentpres- sure data to disk file WriteConvToDisk Boolean Write the currentconversion data to disk file

18. ErrorHandler class Property Table: Name Access Description/CommentsClsName Get Class Name LogFile Get/Let Log file for error messagesMethod Table: Argument Return Name List Type Description SaveConfgBoolean OpenLogFile iFileNo Boolean Open log file with specified filenumber for APPEND, lock WRITE OpenLogfile iFileNo Boolean Open log filewith specified file number for APPEND, lock WRITE CloseLogFile LogErrorsModName, Write error messages to the log sFuncName, file, also callDisplayError in iErrNo, debug mode sErrText DisplayError sModName, Showmessage Box to display sFuncName, the error iErrNo, sErrText

Suitable processors include, by way of example, both general and specialpurpose microprocessors. Generally, a processor will receiveinstructions and data from a read-only memory and/or a random accessmemory. Storage devices suitable for tangibly embodying computer programinstructions and data include all forms of non-volatile memory,including by way of example semiconductor memory devices, such as EPROM,EEPROM, and flash memory devices; magnetic disks such as internal harddisks and removable disks; magneto-optical disks; and CD-ROM disks. Anyof the foregoing can be supplemented by, or incorporated in, ASICs(application-specific integrated circuits).

To provide for interaction with a user, the invention can be implementedon a computer system having a display device such as a monitor or LCDscreen for displaying information to the user and a keyboard and apointing device such as a mouse or a trackball by which the user canprovide input to the computer system. The computer system can beprogrammed to provide a graphical user interface through which computerprograms interact with users.

An example of one such type of computer is shown in FIG. 67, which showsa block diagram of a programmable processing system 1950 suitable forimplementing or performing the apparatus or methods of the invention.The system 1950 includes a processor 1952, a random access memory (RAM)1954, a program memory 1956 (for example, a writable read-only memory(ROM) such as a flash ROM), a hard drive controller 1958, and aninput/output (I/O) controller 1960 coupled by a processor (CPU) bus1962. The system 1950 can be preprogrammed, in ROM, for example, or itcan be programmed (and reprogrammed) by loading a program from anothersource (for example, from a floppy disk, a CD-ROM, or another computer).

The hard drive controller 1958 is coupled to a hard disk 1964 suitablefor storing executable computer programs, including programs embodyingthe present invention, and data including the images, masks, reduceddata values and calculated results used in and generated by theinvention. The I/O controller 1960 is coupled by means of an I/O bus1966 to an I/O interface 1968. The I/O interface 1968 receives andtransmits data in analog or digital form over communication links suchas a serial link, local area network, wireless link, and parallel link.Also coupled to the I/O bus 1966 is a display 1970 and a keyboard 1972.Alternatively, separate connections (separate buses) can be used for theI/O interface 1966, display 1970 and keyboard 1972.

The invention has been described in terms of particular embodiments.Other embodiments are within the scope of the following claims. Althoughelements of the invention are described in terms of a softwareimplementation, the invention may be implemented in software or hardwareor firmware, or any combination of the three. In addition, the steps ofthe invention can be performed in a different order and still achievedesirable results.

Moreover, the above description is intended to be illustrative and notrestrictive. Many embodiments and many applications besides the examplesprovided will be apparent to those of skill in the art upon reading theabove description. The scope of the invention should therefore bedetermined, not with reference to the above description, but shouldinstead be determined with reference to the appended claims, along withthe full scope of equivalents to which such claims are entitled. Thedisclosures of all articles and references, including patentapplications and publications, are incorporated by reference for allpurposes.

What is claimed is:
 1. A method of making and characterizing materials,comprising: forming chemical reaction mixtures in a plurality of reactorvessels of a parallel reactor apparatus, said apparatus comprisingsensors for providing measured values relating to chemical reactions insaid reactor vessels, and a processor for receiving data relating tosaid measured values; confining the reaction mixture in each reactorvessel against fluid communication with the other vessels and at apressure other than ambient pressure; injecting a fluid into at leastone of the reactor vessels while the reaction mixture in said at leastone vessel is confined and at a pressure other than ambient pressure;agitating the reaction mixtures for at least a portion of the confiningstep; and using the processor to receive said date relating to saidmeasured values of the chemical reactions in said reactor vessels.
 2. Amethod as set forth in claim 1 wherein the reaction mixtures of saidreactor vessels are agitated at the same time.
 3. A method as set forthin claim 1 wherein said processor simultaneously receives data relatingto said measured values of chemical reactions occurring in said reactorvessels.
 4. A method as set forth in claim 1 wherein each reactor vesselhas an overall capacity in a range of from about 1 ml to about 500 ml.5. A method as set forth in claim 1 wherein said reaction mixtures areconfined at pressures in a range of from about 10 psig to about 300psig.
 6. A method as set forth in claim 1 wherein said reaction mixturesare confined at pressures in a range of from about 10 psig to about 500psig.
 7. A method as set forth in claim 1 wherein fluid is injected intosaid at least one reactor vessel while the reaction mixture confinedtherein is at a pressure greater than about 10 psig.
 8. A method as setforth in claim 1 wherein fluid is injected into fill ports of thereactor vessels.
 9. A method as set forth in claim 1 further comprisingusing said processor to compare the measured values.
 10. A method as setforth in claim 9 wherein said processor compares said measured values topredetermined parameters.
 11. A method as set forth in claim 9 whereinsaid processor compares measured values relating to one reactor vesselto measured values relating to another reactor vessel.
 12. A method asset forth in claim 9 further comprising using the processor to change anenvironmental condition in at least one of the reactor vessels inresponse to comparing the measured values.
 13. A method as set forth inclaim 9 further comprising using the processor to change the agitationin at least one reactor vessel in response to comparing the measuredvalues.
 14. A method as set forth in claim 1 further comprising usingthe processor to display the measured values.
 15. A method as set forthin claim 1 further comprising using the processor to control thechemical reactions in said vessels in response to said measured values.16. A method as set forth in claim 1 further comprising inputting datarelating to said chemical reactions into the processor using a userinterface.
 17. A method as set forth in claim 16 further comprisingcontrolling an environmental condition in at least one reactor vessel byusing said user interface.
 18. A method as set forth in claim 17 whereinsaid environmental condition is the temperature of the reaction mixtureconfined in at least one reactor vessel.
 19. A method as set forth inclaim 17 wherein said environmental condition is the pressure at whichthe reaction mixture is confined in at least one reactor vessel.
 20. Amethod as set forth in claim 16 further comprising controlling theagitation of said reaction mixtures in at least one reactor vessel byusing said user interface.
 21. A method as set forth in claim 16 furthercomprising controlling the injection of fluid into at least one reactorvessel by using said user interface.
 22. A method as set forth in claim1 further comprising placing at least two liners in two separate wellsin a single reactor block.
 23. A method as set forth in claim 1 whereinsaid fluid is injected using a robotic probe movable between reactorvessels.
 24. A method as set forth in claim 1 wherein said reactionmixtures are agitated by rotating a stirring member in each of saidreactor vessels.
 25. A method of making and characterizing materials,comprising: forming chemical reaction mixtures in a plurality of reactorvessels of a parallel reactor apparatus, said apparatus comprisingsensors for providing measured values relating to chemical reactions insaid reactor vessels, and a processor for receiving and displaying datarelating to said measured values; confining the reaction mixture in eachreactor vessel against fluid communication with the other vessels and ata pressure other than ambient pressure; injecting a fluid into at leastone of the reactor vessels while the reaction mixture in said at leastone vessel is confined and at a pressure other than ambient pressure;agitating the reaction mixtures for at least a portion of the confiningstep; using the processor to receive and display said data relating tosaid measured values; and comparing at least one characteristic of thechemical reactions in the reactor vessels based on said data.
 26. Amethod as set forth in claim 25 wherein fluid is injected into fillports of the reactor vessels.
 27. A method as set forth in claim 25wherein each reactor vessel has an overall capacity in a range of fromabout 1 ml to about 500 ml.
 28. A method as set forth in claim 25wherein said reaction mixtures are confined at pressures in a range offrom about 10 psig to about 300 psig.
 29. A method as set forth in claim25 wherein said reaction mixtures are confined at pressures in a rangeof from about 10 psig to about 500 psig.
 30. A method as set forth inclaim 25 wherein fluid is injected into said at least one reactor vesselwhile the reaction mixture confined therein is at a pressure greaterthan about 10 psig.
 31. Apparatus for the parallel processing ofreaction mixtures, comprising: a plurality of sealed reactor vessels forholding reaction mixtures; a temperature control system for regulatingthe temperature of the reaction mixtures in the reactor vessels; aninjection system for introducing chemical reaction materials into one ormore of said sealed reactor vessels while the reactor vessel is at apressure other than ambient pressure; a mechanism for agitating thereaction mixture in each of the sealed reactor vessels; sensors forproviding measured values relating to chemical reactions in said reactorvessels; and a processor for receiving and comparing data relating tosaid measured values.
 32. Apparatus as set forth in claim 31 whereineach reactor vessel has an overall capacity in a range of about 1 ml toabout 500 ml.
 33. Apparatus as set forth in claim 31 wherein saidreaction mixtures are confined in said sealed vessels at pressures in arange of from about 10 psig to about 300 psig.
 34. Apparatus as setforth in claim 31 wherein said reaction mixtures are confined in saidsealed vessels at pressures in a range of from about 10 psig to about500 psig.
 35. Apparatus as set forth in claim 31 wherein said injectionsystem comprises a fluid delvery probe, said injection system beingoperable for preventing leakage of fluid under pressure from a vesselafter said introduction by said fluid delivery probe.
 36. Apparatus asset forth in claim 35 wherein said injection system comprises a fillport or each reactor vessel.
 37. Apparatus as set forth in claim 31wherein said mechanism for agitating comprises a stirring member insideeach reactor vessel.
 38. Apparatus as set forth in claim 37 wherein saidmechanism for agitating comprises a single motor for moving the stirringmembers in said reactor vessels.
 39. Apparatus as set forth in claim 31wherein said reactor vessels are removable liners in a group of wellsfor holding said reaction mixtures, the liners and reaction mixturestherein being removable from the wells.
 40. Apparatus as set forth inclaim 31 wherein said processor includes a display for displaying saiddata.
 41. Apparatus as set forth in claim 31 further comprising a commonhousing for said vessels.
 42. Apparatus as set forth in claim 31 furthercomprising a common base for said vessels.
 43. Apparatus as set forth inclaim 31 wherein said vessels are grouped in an array sized for benchscale use.
 44. Apparatus for the parallel processing of reactionmixtures, comprising: a plurality of sealed reactor vessels for holdingreaction mixtures; temperature control means for regulating thetemperature of the reaction mixtures in the reactor vessels; injectionmeans for introducing chemical reaction materials into one or more ofsaid sealed reactor vessels; means for agitating the reaction mixture ineach of said sealed reactor vessels; means for sensing measured valuesrelating to chemical reactions in said reactor vessels; and means forreceiving and comparing data relating to said measured values. 45.Apparatus for the parallel processing of reaction mixtures, comprising;a plurality of sealed reactor vessels for holding reaction mixtures;temperature control means for regulating the temperature of the reactionmixtures in the reactor vessels; injection means for introducingchemical reaction materials into one or more of said sealed reactorvessels; means for agitating the reaction mixture in each of said sealedreactor vessels; means for sensing measured values relating to chemicalreactions in said reactor vessels; and means for receiving anddisplaying data relating to said measured values.
 46. Apparatus as setforth in claim 45 wherein said means for receiving and displaying isfurther operable to compare at least one characteristic of the chemicalreactions in the reactor.
 47. Apparatus as set forth in claims 44 or 45wherein each reactor vessel has an overall capacity in a range of about1 ml to about 500 ml.
 48. Apparatus as set forth in claims 44 or 45wherein said reaction mixtures are confined in said sealed vessels atpressures in a range of from about 10 psig to about 300 psig. 49.Apparatus as set forth in claims 44 or 45 wherein said reaction mixturesare confined in said sealed vessels at pressures in a range of fromabout 10 psig to about 500 psig.
 50. Apparatus as set forth in claims 44or 45 wherein said injection means comprises a fluid delivery probe,said injection means being operable for preventing leakage of fluidunder pressure from a vessel after said introduction by said fluiddelivery probe.
 51. Apparatus as set forth in claim 50 wherein saidinjection means comprises a fill port for each reactor vessel. 52.Apparatus as set fourth in claims 44 or 45 wherein said means foragitating comprises a stirring member inside each reactor vessel. 53.Apparatus as set forth in claim 52 wherein said means for agitatingcomprises a single motor for moving the stirring members in said reactorvessels.
 54. Apparatus as set forth in claims 44 or 45 wherein saidreactor vessels comprise removable liners in a group of wells forholding said reaction mixtures, the liners and reaction mixtures thereinbeing removable from the wells.
 55. Apparatus as set forth in claims 44or 45 further comprising a common housing for said vessels. 56.Apparatus as set forth in claims 44 or 45 further comprising a commonbase for said vessels.
 57. Apparatus as set forth in claims 44 or 45wherein said vessels are grouped in an array sized for bench scale use.